- Email: [email protected]
Assessing the Utility of Post-Mastectomy Imaging after Breast Reconstruction
Journal Pre-proof Assessing the Utility of Post-Mastectomy Imaging after Breast Reconstruction Ronnie L. Shammas, MD, Gloria Broadwater, MS, Roger W. Cason, MD, Adam D. Glener, MD, Amanda R. Sergesketter, MD, Rebecca Vernon, BS, Eliot Le, BS, Tori Wickenheisser, BS, Caitlin Marks, BS, Scott T. Hollenbeck, MD, FACS PII:
S1072-7515(20)30114-9
DOI:
https://doi.org/10.1016/j.jamcollsurg.2020.01.006
Reference:
ACS 9723
To appear in:
Journal of the American College of Surgeons
Received Date: 11 December 2019
Please cite this article as: Shammas RL, Broadwater G, Cason RW, Glener AD, Sergesketter AR, Vernon R, Le E, Wickenheisser T, Marks C, Hollenbeck ST, Assessing the Utility of Post-Mastectomy Imaging after Breast Reconstruction, Journal of the American College of Surgeons (2020), doi: https:// doi.org/10.1016/j.jamcollsurg.2020.01.006. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons.
Assessing the Utility of Post-Mastectomy Imaging after Breast Reconstruction Ronnie L Shammas, MD1, Gloria Broadwater, MS2, Roger W Cason, MD1, Adam D Glener, MD1, Amanda R Sergesketter, MD1, Rebecca Vernon, BS1, Eliot Le, BS1, Tori Wickenheisser, BS1, Caitlin Marks, BS1, Scott T Hollenbeck, MD, FACS1 1
Division of Plastic, Maxillofacial, and Oral Surgery, Department of Surgery, Duke University Health System, Durham, NC 2 Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University Medical Center, Durham, NC Disclosure Information: Nothing to disclose. Presented at the Southern Surgical Association 131th Annual Meeting, Hot Springs, VA, December 2019.
Corresponding Author Contact Information: Scott T Hollenbeck, MD Associate Professor, Division of Plastic and Reconstructive Surgery Duke University Medical Center Box 3945 Durham, NC 27710, USA Phone: (919) 681-5079 | Fax: (919) 681-2670 Email: [email protected]
Brief Title: Post-Mastectomy Imaging and Breast Reconstruction
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BACKGROUND: Few guidelines exist regarding surveillance and diagnostic imaging after breast reconstruction. This study investigates the influence of breast reconstruction on the frequency of post-mastectomy imaging, the relative utility of imaging, and its effect on overall and locoregional recurrence-free survival. STUDY-DESIGN: A retrospective review identified breast cancer patients (n=1216) who underwent mastectomy with or without reconstruction. Logistic regression identified surgical and oncologic predictors of post-reconstruction imaging. Kaplan-Meier methods determined the impact of post-reconstruction imaging on overall and locoregional recurrence-free survival. RESULTS: Overall, 662 (54.4%) patients underwent mastectomy only and 554 (45.6%) underwent breast reconstruction. Patients undergoing reconstruction were more likely to receive imaging compared to patients undergoing mastectomy only (n=205, 37.0% vs. n=168, 25.4%; p<.0001); however, this difference was not statistically significant after adjusting for age and follow-up time (p=0.16). Most radiographic studies were BI-RADS 1 (n=58, 30%) or 2 (n=95, 49%) and were ordered by non-surgical providers (n=128, 63%). Post-reconstruction imaging did not influence overall or locoregional recurrence-free survival. The 5-year survival probability for breast reconstruction patients who underwent imaging for a palpable mass, surveillance, or who did not undergo imaging was 100%, 95% (95% CI:89-100%), and 96% (95% CI: 94-99%), respectively. Post-reconstruction imaging was not a significant predictor of overall survival (HR, 0.95; 95% CI 0.61-1.46; p=0.30) CONCLUSION: The limited utility of routine post-reconstruction imaging should be reinforced when evaluating breast reconstruction patients. Multidisciplinary collaboration should be emphasized when attempting to distinguish benign post-surgical findings from a malignant process to reduce unnecessary imaging and biopsies following breast reconstruction.
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INTRODUCTION Breast cancer remains one of the most common malignancies worldwide,1 with mastectomy rates continuing to rise.2 This has been paralleled by an increase in both autologous and implant-based breast reconstruction.3 Currently, the National Comprehensive Cancer Network (NCCN) recommends against the routine imaging of breast cancer patients who have had a mastectomy with or without breast reconstruction.4 Despite this, there remains no consensus amongst surgeons, oncologists, and radiologists regarding routine or diagnostic imaging in breast reconstruction patients. The incidence of locoregional recurrence after mastectomy has been reported to be between 1% and 10%5-8, with most recurrences occurring within 5 years of mastectomy. Historically, physical exam was the ideal method for detecting locoregional recurrence. However, recent advancements in breast reconstruction, such as pre-pectoral implant placement, have introduced concern about the effects of prosthetic or autologous breast reconstruction on the detection of superficial or chest wall recurrences. Despite previous studies that have reported on the limited utility of surveillance or diagnostic imaging following autologous breast reconstruction, there remains no consensus amongst providers regarding the appropriate use of post-mastectomy imaging in the reconstructed patient.7, 9, 10 Furthermore, the potential for breast reconstruction to impair the utility of physical exam to detect locoregional recurrences, in addition to the increased incidence of benign physical exam findings such as cystic lesions and fat necrosis, may lower the threshold for imaging after mastectomy.11 The goal of this study was to examine the influence of implant or autologous breast reconstruction on post-mastectomy imaging, and the utility of diagnostic or surveillance imaging following breast reconstruction. We hypothesized that a large proportion of breast reconstruction
3
patients would be imaged following mastectomy and that imaging would not confer an improvement in overall or locoregional recurrence-free survival. METHODS Study Design A retrospective review was performed on all adult female patients who were diagnosed with breast cancer and underwent mastectomy with or without breast reconstruction from 20102018 at Duke University Medical Center. Patients were categorized into two study groups: 1) Those who underwent mastectomy without breast reconstruction and 2) Those who underwent mastectomy with implant or autologous breast reconstruction. Exclusion criteria included patients who underwent a partial mastectomy or lumpectomy, combined autologous and implant reconstruction, those with incomplete or missing information from the patient record, and patients who had an initial diagnosis of stage IV cancer. In addition, patients were excluded if they did not carry a cancer diagnosis. A CONSORT diagram displaying study selection criteria is shown in Figure 1. Definition of Variables Independent variables analyzed in this study included age at mastectomy, follow-up time, race, ethnicity, BMI, diabetes, smoking status, cancer stage, TNM stage, chemotherapy type (adjuvant, neoadjuvant, no chemotherapy), radiation type (adjuvant, neoadjuvant, or no radiation), type of mastectomy, surgical laterality, hormone receptor status, human epidermal growth factor receptor-2 status (HER-2), BRCA status, the presence of locoregional recurrence, and overall survival. Specific reconstructive variables analyzed included timing of reconstruction (immediate or delayed), type of breast reconstruction (implant or autologous), and the use of fat grafting. With respect to radiographic variables, three forms of imaging were analyzed. These
4
included ultrasound, magnetic resonance imaging (MRI), and mammography. Specific radiographic variables included the total number of post-mastectomy imaging events, Breast Imaging Reporting and Data System (BI-RADS) scores, indication for imaging (surveillance or palpable mass on clinical exam), number of biopsies, radiologic interpretations of imaging, pathologic interpretations, and provider who ordered the imaging. Briefly, BI-RADS scores of 1 are considered negative, 2 are benign, 3 are probably benign, 4 are suspicious, 5 are highly suggestive of malignancy, and 6 are assigned to lesions of known biopsy-proven malignancy.12 Providers were categorized into five categories: primary care provider (PCP), breast surgeon, breast oncologist, plastic surgeon, or other. Locoregional recurrence was defined as that which occurred within the skin or chest wall of the breast. Patients who developed distant metastasis following mastectomy were not considered to have locoregional recurrence. Study Outcomes The primary endpoint for this study was receipt of imaging following mastectomy. Imaging tests in the form of MRI, ultrasonography, or mammography, that were performed on the post-mastectomy breast were considered an imaging event. In the instance of unilateral breast cancer, imaging of the intact, non-cancerous breast was not considered in the analysis. Secondary endpoints included overall and locoregional recurrence-free survival from the date of mastectomy. Statistical Analysis Categorical variables and proportions were compared using chi-square tests. T-tests and Wilcoxon rank sum tests compared continuous factors depending on the distribution of the data, and logistic regression models predicted receipt of imaging. Kaplan-Meier methods were used to estimate time to locoregional recurrence and time to death. Cox proportional hazards regression
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was used to adjust for covariates while testing the predictability of post-reconstruction imaging on overall survival. P-values <0.05 were considered statistically significant. Analyses were conducted using SAS software (V 9.4; SAS Institute Inc., Cary, NC). Graphs were produced by R software (R Foundation for Statistical Computing, Vienna, Austria). RESULTS Patient population A total of 1,216 patients were analyzed after all exclusions. Of these 662 (54.4%) patients underwent mastectomy only and 554 (45.6%) underwent mastectomy with breast reconstruction. Of those undergoing breast reconstruction, 315 (56.9%) underwent autologous reconstruction and 239 (43.1%) underwent implant reconstruction. The baseline unadjusted characteristics of all patients categorized by those who did and did not undergo breast reconstruction are shown in eTable 1. Overall, the mean age of the study cohort was 57.4 (SD ± 13.39) years. Patients who underwent breast reconstruction were predominately of White race, younger, had fewer medical comorbidities, and had positive hormone receptor (ER/PR) and HER-2 receptor status cancers. The baseline characteristics of all patients who underwent breast reconstruction, categorized by reconstruction type (implant based or autologous), are shown in Table 1. Patients who underwent autologous breast reconstruction tended to have a higher BMI, were more likely to undergo delayed reconstruction, receive neoadjuvant chemotherapy and adjuvant radiation therapy, and undergo fat grafting. Association of Breast Reconstruction and Post-Mastectomy Imaging A total of 373 patients (30.7%) underwent a form of post-mastectomy imaging. On univariate analysis, patients who underwent autologous or implant-based breast reconstruction (n=205, 37.0%) underwent post-mastectomy imaging more frequently than mastectomy only
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patients (n=168, 25.4%) (p<.0001). Given these observed differences, we then assessed which oncologic and surgical factors may predispose breast reconstruction patients to imaging following mastectomy. As shown in Table 2, univariate logistic regression revealed that younger age at mastectomy (OR, 0.68; 95% CI 0.56-0.82; p<.0001), longer follow-up time (OR, 6.50; 95% CI 3.14-13.45; p<.0001), palpable mass (p<.0001), and fat grafting (OR, 0.66; 95% CI 0.46-0.97) were significantly associated with an increased likelihood for post-mastectomy imaging. Notably, reconstruction type (autologous vs. implant), tumor stage, and the receipt of chemotherapy or radiation therapy were not predictive of post-mastectomy imaging. Multivariate logistic regression analysis indicated that after adjustment for covariates, only a younger age at mastectomy (OR, 0.75; 95% CI 0.59-0.967; p=0.026), increased length of follow up (OR, 6.72; 95% CI 2.75-16.41; p<.0001) and palpable mass (p<.0001) were independently predictive of imaging following mastectomy. Characteristics of Post-Mastectomy Imaging Following Breast Reconstruction The overall characteristics of the post-reconstruction imaging events are shown in Table 3. Given the relatively high incidence of post-reconstruction imaging, radiologic and pathologic interpretations of imaging and biopsies were analyzed to determine the relative utility of diagnostic or surveillance imaging in the reconstructed patient. Of the 205 reconstructed patients imaged, 119 received autologous reconstruction and 86 had implant-based reconstruction. Breast reconstruction patients received a total of 398 imaging events. Of these, autologous reconstruction patients underwent 262 (median 2.0) imaging events compared to 136 (median 1.0) in implant-based reconstruction (p=0.004). With respect to imaging modality, most breast reconstruction patients underwent a combination of mammogram and ultrasound. There was no significant difference in the frequency of post-mastectomy imaging for indications of
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surveillance or for the evaluation of a palpable mass (n=95, 47.5% vs. n=105, 52.5%; p=0.98). When assessing which provider ordered the imaging study, most were ordered by the breast oncologist (n=128, 62.7%), while a minority were ordered by the breast surgeon (n=37, 18.1%) or plastic surgeon (n=8, 3.9%). Most imaging studies performed on breast reconstruction patients were considered “negative” or “benign” and received a BI-RADS score of 1 (n=58, 29.9%) or 2 (n=95, 49.0%). A total of 28 studies (14.4%) were interpreted as suspicious and were assigned a BI-RADS score of 4. Forty-seven patients (22.9%) underwent biopsies, with a total of 52 biopsies performed amongst breast reconstruction patients. There was no significant difference in the number of patients in which biopsies were performed when comparing autologous or implant-based reconstruction (n=27, 22.7% vs. n=20, 23.3%; p=0.92). With respect to radiologic and pathologic interpretations of imaging and biopsies, most findings were interpreted as benign post-surgical changes (n=103, 50.5%) or fat necrosis (n=33, 16.2%). In addition, patients who underwent autologous breast reconstruction more frequently had evidence of fat necrosis on imaging or biopsy. Out of a total of 9 locoregional recurrences that were detected amongst breast reconstruction patients, 5 were detected by imaging or biopsy. The remaining 4 were detected by physical exam and confirmed on pathology with surgical excision. Impact of Imaging After Breast Reconstruction on Overall and Locoregional Recurrence-Free Survival Kaplan-Meier curves were used to estimate the overall survival rates of breast reconstruction patients for those who did and did not undergo post-mastectomy imaging for indications of surveillance or the finding of a palpable mass on exam. Figure 2A represents the comparison of overall survival, and Figure 2B represents the comparison of locoregional
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recurrence-free survival between breast reconstruction patients who underwent post-mastectomy imaging for a palpable mass or surveillance, and those who did not undergo imaging. Breast reconstruction patients who underwent imaging for surveillance, or for a palpable mass, displayed no clinically meaningful difference in overall survival as compared to breast reconstruction patients who did not undergo imaging. In addition, there was no clinically meaningful difference in locoregional recurrence-free survival when comparing patients who did or did not undergo imaging for indications of surveillance or the detection of a palpable mass. The overall 5-year survival probability for breast reconstruction patients who underwent imaging for indications of a palpable mass or surveillance, and those who did not undergo imaging was 100%, 95% (95% CI: 89-100%), and 96% (95% CI: 94-99%), respectively. Among those who received imaging for indications of a palpable mass or surveillance, and those who did not receive post-mastectomy imaging, the 5-year locoregional recurrence-free probability was 95% (95% CI: 90-99%), 99% (95% CI: 97-100%), and 99% (95% CI: 97-100%), respectively. A Cox proportional hazard model was used to assess the effect of post-mastectomy imaging on overall survival amongst breast reconstruction patients. After adjusting for age at mastectomy and follow-up time, post-mastectomy imaging was not found to be a significant predictor of overall survival (HR, 0.95; 95% CI 0.61-1.46; p=0.30). DISCUSSION In this retrospective review, a noteworthy proportion of breast reconstruction patients underwent imaging or biopsy following mastectomy. Furthermore, younger patients were more likely to undergo imaging after breast reconstruction, despite most imaging and biopsies resulting in a benign finding. When assessing the impact of post-mastectomy imaging on
9
survival, imaging in the reconstructed patient for indications of surveillance or a palpable mass did not affect overall or locoregional recurrence-free survival. While the rates of post-mastectomy breast reconstruction continue to rise, there remains no consensus regarding the use of routine or diagnostic breast imaging in the reconstructed patient.13, 14 Currently, the gold standard for monitoring the development of locoregional recurrence is physical examination. However, advanced reconstructive techniques that cover the chest wall and result in the appearance of a near normal-appearing breast, have resulted in increased uncertainty amongst providers regarding the need for surveillance imaging. Furthermore, the increased incidence of benign physical exam findings, such as oil cysts and fat necrosis, may increase the frequency of post-mastectomy imaging and biopsy in the reconstructed patient. Our findings suggest that post-mastectomy imaging for indications of routine surveillance has limited utility, and that imaging for indications of surveillance or the detection of a palpable mass have limited effect on overall or locoregional-recurrence free survival following breast reconstruction. Increased emphasis should be placed on physical examination as a surveillance strategy, and multidisciplinary communication should be emphasized to better define the likelihood of a benign physical exam finding due to reconstructive techniques and reduce the incidence of unnecessary imaging and biopsy after mastectomy. The overwhelming consensus amongst providers is that there is little utility in surveillance imaging to detect locoregional recurrence after mastectomy.15, 16 However, no such consensus exists for patients undergoing breast reconstruction. Initial concerns that breast reconstruction may impede the detection of locoregional recurrence, or stimulate dormant disease with the transfer of autologous tissue have remained unfounded.17, 18 Reddy et al.
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reported that the incidence and time to detection of locoregional recurrence did not differ in patients who did or did not undergo reconstruction.17 Furthermore, when examining the role of surveillance imaging in a seemingly normal appearing breast following implant or autologous breast reconstruction, Zakhireh et al. emphasized that there is insufficient evidence to recommend annual mammograms over physical examination for the detection of locoregional recurrence.5-7, 9, 10, 19 In a study by Noroozian et al., which reviewed 515 patients who had undergone autologous breast reconstruction and mammographic surveillance, the oncologic safety of breast reconstruction was re-demonstrated with locoregional recurrence reported as 3.9% (20 of 515 women). While mammogram did aid in the detection of clinically occult disease, the majority of locoregional recurrences could be detected with physical examination.19 Despite previously published work demonstrating the limited utility of mammography following breast reconstruction, our study demonstrates that a large proportion of breast reconstruction patients are subject to frequent imaging in the form of ultrasonography, mammography, or MRI, with a large proportion of these patients still undergoing imaging for the purposes of cancer surveillance. The rate of locoregional recurrence reported in this study (1.6%) following breast reconstruction is consistent with prior reports17 and reinforces the oncologic safety of reconstructive techniques. With respect to radiologic findings and pathologic interpretations following biopsy, most suspected abnormalities were determined to be benign lesions. Often, these were classified as normal post-surgical changes or fat necrosis. Palpable lumps after fat grafting due to fat necrosis are known to be a common occurrence following breast reconstruction.20 Consequently, as reconstructive techniques advance and the use of fat grafting continues to increase,21 defining the optimum surveillance strategy for the associated palpable abnormalities has become increasingly important. Based on our results, we suggest that
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palpable masses in the reconstructed population who have recently undergone fat grafting may be conservatively managed with surveillance via physical examination. The workup of a post-reconstructive breast lesion should be considered in a multidisciplinary setting. Prior studies have shown that knowledge deficits and differences in goals of care exist between medical oncology and plastic surgery when considering complications and diagnostic workups.22 The results of our study found that within the authors’ institution, most imaging studies in the reconstructed patient were ordered by the medical oncology team, while a minority tended to be ordered by the breast surgeon and/or plastic surgeon. This may be partially attributed to a lack of appropriate communication amongst providers when attempting to distinguish expected physical exam findings following breast reconstruction (i.e. fat necrosis) from a malignant process. Furthermore, as emphasized in this study and others, the use of imaging for indications of surveillance, or for the evaluation of a palpable mass, does not improve overall survival or locoregional recurrence-free survival when compared to breast reconstruction patients who do not undergo imaging.9, 10, 17-19 The limited utility of routine imaging should be emphasized in the evaluation of a breast reconstruction patient; and improved multidisciplinary communication should be implemented when attempting to distinguish benign post-surgical findings from a malignant processes in order to reduce unnecessary imaging and biopsies following breast reconstruction. Study Limitations This study is limited by its retrospective design. Similar to other studies, patients who underwent mastectomy without reconstruction tended to represent an older population of women with more aggressive tumor types and treatment courses, and shorter lengths of follow-up and overall survival.10, 17 In addition, while the rates of locoregional recurrence in this study are
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similar to those previously reported,17 the low number precludes any meaningful statistical conclusions that can be drawn when comparing patients who did and did not undergo reconstruction and developed a locoregional recurrence. Although this study represents the largest cohort of cancer patients who did and did not undergo breast reconstruction, a multiinstitutional study is needed to make an adequate statistical comparison of patients when considering the development of locoregional recurrence. However, the focus of this study was not to evaluate locoregional recurrence, but rather to examine the relative utility of imaging in breast reconstruction patients. CONCLUSION To date, there remains no standardized consensus regarding the appropriate surveillance strategy for recurrence in the reconstructed patient. Our study revealed that overall, breast reconstruction patients are more frequently imaged following mastectomy, and younger age is independently predictive of post-mastectomy imaging. Most radiologic and pathological results were reported as benign findings, and most studies were not ordered by the surgical team. Furthermore, post-mastectomy imaging in the breast reconstruction patient for indications of a palpable mass or for surveillance did not affect overall survival or disease-free survival. Overall, these findings emphasize the need for improved communication across subspecialties to minimize the incidence of unnecessary imaging and biopsy in the reconstructed patient. Future prospective studies are needed to further define the role of mammography and ultrasound following breast reconstruction to determine the benefits of imaging on oncologic outcomes.
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Précis Breast reconstruction patients undergo post-mastectomy imaging more frequently than mastectomy only patients. Post-reconstruction imaging for indications of a palpable mass or surveillance did not affect overall or disease-free survival. Improved multidisciplinary communication is needed to minimize the incidence of unnecessary imaging and biopsy in the reconstructed patient.
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Table 1. Patient Characteristics for Reconstructed Subset by Type of Reconstruction
Variable Age at oncologic mastectomy, y, mean (SD) Follow-up, y, mean (SD) Race/ethnicity, n (%) White African American Hispanic/Latino Other or unspecified Missing, n BMI at mastectomy, n (%) <25 kg/m2 25-30 kg/m2 >30 kg/m2 Missing, n Diabetes, n (%) Smoker, n (%) Tumor stage, n (%) 0 I IIA IIB IIIA IIIB IIIC Neoadjuvant chemotherapy, n (%) Adjuvant chemotherapy, n (%) Neoadjuvant RT, n (%) Adjuvant RT, n (%) Mastectomy type, n (%) Nipple sparing Skin sparing Simple Modified radical Radical Missing, n Mastectomy laterality, n (%) Unilateral Bilateral Missing, n Reconstruction timing, n (%) Immediate
Type of reconstruction performed? Autologous Implant-based (n=316) (n=241) 50.0 (8.57) 50.3 (11.01)
Total (n=557)
p Value
50.1 (9.69)
0.6707* 0.7117* 0.4959†
4.0 (2.63)
4.0 (2.54)
4.0 (2.59)
235 (74.6) 60 (19.0) 2 (0.6) 18 (5.7) 0
177 (74.4) 43 (18.1) 5 (2.1) 13 (5.5) 1
412 (74.5) 103 (18.6) 7 (1.3) 31 (5.6) 1 <.0001†
65 (21.3) 113 (37.0) 127 (41.6) 10 29 (9.2) 20 (6.3)
90 (41.1) 65 (29.7) 64 (29.2) 20 17 (7.1) 8 (3.3)
155 (29.6) 178 (34.0) 191 (36.5) 30 46 (8.3) 28 (5.1)
72 (22.9) 82 (26.0) 59 (18.7) 43 (13.7) 39 (12.4) 8 (2.5) 12 (3.8) 108 (35.0) 93 (30.4) 21 (6.8) 132 (43.4)
58 (24.3) 79 (33.1) 58 (24.3) 24 (10.0) 15 (6.3) 3 (1.3) 2 (0.8) 41 (17.4) 80 (34.3) 2 (0.9) 51 (21.8)
130 (23.5) 161 (29.1) 117 (21.1) 67 (12.1) 54 (9.7) 11 (2.0) 14 (2.5) 149 (27.3) 173 (32.1) 23 (4.2) 183 (34.0)
27 (8.6) 40 (12.8) 170 (54.3) 75 (24.0) 1 (0.3) 2
59 (24.7) 31 (13.0) 132 (55.2) 17 (7.1) 0 (0.0) 0
86 (15.6) 71 (12.9) 302 (54.7) 92 (16.7) 1 (0.2) 2
187 (59.6) 127 (40.4) 1
98 (41.0) 141 (59.0) 0
285 (51.5) 268 (48.5) 1
108 (34.4)
193 (81.1)
301 (54.5)
0.3765† 0.1102† 0.0095†
<.0001† 0.3314† 0.0006† <.0001† <.0001†
<.0001†
<.0001†
18
Delayed Missing, n ER+, n (%) PR+, n (%) HER2+, n (%) Triple negative, n (%) Fat grafting, n (%) Breast imaging after mastectomy, n (%)
206 (65.6) 1 237 (75.2) 208 (66.0) 68 (21.6) 48 (15.2) 119 (37.9) 119 (37.8)
45 (18.9) 1 192 (80.3) 158 (66.1) 51 (21.3) 30 (12.6) 43 (18.3) 86 (36.0)
251 (45.5) 2 429 (77.4) 366 (66.1) 119 (21.5) 78 (14.1) 162 (29.5) 205 (37.0)
0.1552† 0.9849† 0.9438† 0.3680† <.0001† 0.6648†
*
t-test †Chi-Square test; RT, radiation therapy
19
Variable, comparison
Odds ratio
Lower confidence limit
Upper confidence limit
Age at mastectomy 10-year increase
<.0001 0.680
0.564
0.819
Reconstruction type Autologous vs implant
0.665 1.080
0.762
1.531
Race
0.244
White vs African American
1.268
0.815
1.972
White vs Hispanic
0.737
0.141
3.844
White vs other
1.964
0.944
4.087
Diabetes Yes vs no
0.994 1.002
0.536
1.873
Smoker Yes vs no
0.797 0.903
0.414
1.968
Tumor stage
0.118
Stage 3 vs 0
0.640
0.355
1.153
Stage 3 vs 1
1.161
0.671
2.011
Stage 3 vs 2
0.887
0.516
1.525
Neoadjuvant chemotherapy Yes vs no
0.342 0.829
0.563
1.220
Adjuvant chemotherapy Yes vs no
0.824 0.959
0.660
1.392
Neoadjuvant radiation Yes vs no
0.487 1.378
0.557
3.410
Adjuvant radiation Yes vs no
0.808 0.955
0.661
1.380
BMI category
0.144
25-30 kg/m2 vs < 25 kg/m2
1.122
0.724
1.740
> 30 kg/m2 vs < 25 kg/m2
0.741
0.476
1.153
Laterality of reconstruction Unilateral vs bilateral Years of follow-up
p Value
0.496 0.887
0.627
1.253 <.0001
20
10-year increase
6.495
3.137
13.445
Fat grafting Yes vs no
0.032 0.663
0.456
0.965
Reconstruction timing Immediate vs delayed
0.269 1.216
0.860
1.720
Palpable mass* Yes vs no
<.0001 NA
NA
NA
BRCA status Positive vs negative
0.310 0.752
0.433
1.304
*OR not estimable due to few patients with a palpable mass not imaged NA, not applicable
21
Table 3. Characteristics of Breast Reconstruction Patients Who Underwent Post-Mastectomy Imaging Variable No. of post-mastectomy imaging events Total, n Median (range) Imaging type, n (%) Ultrasound only MRI only Mammogram only > 1 type BI-RADS, n (%) 1 2 3 4 Missing, n Indication for imaging, n (%) Surveillance Palpable mass on exam Missing, n Biopsy performed, n (%) Total no. of biopsies performed to date Total, n Median (range) If a mass was palpated, which occurred? n (%) Imaging followed by biopsy Direct to biopsy Imaging only Radiologic and pathologic interpretation of imaging and biopsy, n (%) Normal Recurrence Fat necrosis Other Multiple Missing Provider who ordered imaging/biopsy, n (%) Primary care provider Breast surgeon Breast oncologist Plastic surgeon Other Multiple
Type of reconstruction performed? Autologous Implant-based (n=119) (n=86)
Total (n=205)
p Value 0.00352
262 2.0 (1.0, 10.0)
136 1.0 (1.0, 5.0)
398 2.0 (1.0, 10.0) 0.25371
20 (16.8) 17 (14.3) 24 (20.2) 58 (48.7)
23 (26.7) 15 (17.4) 15 (17.4) 33 (38.4)
43 (21.0) 32 (15.6) 39 (19.0) 91 (44.4) 0.81621
34 (30.4) 52 (46.4) 8 (7.1) 18 (16.1) 7
24 (29.3) 43 (52.4) 5 (6.1) 10 (12.2) 4
58 (29.9) 95 (49.0) 13 (6.7) 28 (14.4) 11 0.97711
55 (47.4) 61 (52.6) 3 27 (22.7)
40 (47.6) 44 (52.4) 2 20 (23.3)
95 (47.5) 105 (52.5) 5 47 (22.9)
30 1.0 (1.0, 2.0)
22 1.0 (1.0, 2.0)
52 1.0 (1.0, 2.0)
0.92411 0.90382
0.40811 30 (25.2) 1 (0.8) 88 (73.9)
22 (25.5) 2 (2.3) 62 (72.1)
52 (25.3) 3 (1.4) 150 (73.2) 0.04691
51 (42.9) 4 (3.4) 24 (20.2) 17 (14.3) 23 (19.3) 0
52 (61.2) 1 (1.2) 9 (10.6) 14 (16.5) 9 (10.6) 1
103 (50.5) 5 (2.5) 33 (16.2) 31 (15.2) 32 (15.7) 1 0.74671
5 (4.2) 19 (16.1) 77 (65.3) 4 (3.4) 2 (1.7) 11 (9.3)
6 (7.0) 18 (20.9) 51 (59.3) 4 (4.7) 2 (2.3) 5 (5.8)
11 (5.4) 37 (18.1) 128 (62.7) 8 (3.9) 4 (2.0) 16 (7.8)
22
Missing, n
1
0
1
*Chi-square test †Wilcoxon rank-sum test BI-RADS, Breast Imaging Reporting and Data System
23
Figure Legends: Figure 1: CONSORT diagram of patient selection criteria. Figure 2: Kaplan-Meier probability for (A) overall survival and (B) locoregional recurrence-free survival for reconstruction subset.
24
Precis Breast reconstruction patients undergo imaging more frequently than mastectomy only patients. Post-reconstruction imaging for indication of a palpable mass or surveillance did not affect overall or disease-free survival. Improved multidisciplinary communication is needed to minimize unnecessary imaging and biopsy in the reconstructed patient.
25
eTable 1. Patient Characteristics
Variable
Age at oncologic mastectomy, y, mean (SD) Follow up, y, mean (SD) Race/ethnicity, n (%) White African American Hispanic/Latino Other or unspecified Missing, n BMI at mastectomy, n (%) <25 kg/m2 25-30 kg/m2 >30 kg/m2 Missing, n Diabetes, n (%) Smoker, n (%) Tumor stage, n (%) 0 I IIA IIB IIIA IIIB IIIC Neoadjuvant chemotherapy, n (%) Adjuvant chemotherapy, n (%) Neoadjuvant RT, n (%) Adjuvant RT, n (%) Type of mastectomy, n (%) Nipple sparing Skin sparing Simple Modified radical Radical Missing, n Mastectomy laterality, n (%) Unilateral Bilateral
Did the patient undergo reconstruction after mastectomy? No Yes (n=662) (n=554)
Total (n=1216)
p Value
63.5 (13.01)
50.1 (9.69)
57.4 (13.39)
<.0001*
4.0 (2.88)
4.0 (2.59)
4.0 (2.75)
0.8066* <.0001†
404 (61.0) 225 (34.0) 5 (0.8) 28 (4.2) 0
412 (74.5) 103 (18.6) 7 (1.3) 31 (5.6) 1
816 (67.2) 328 (27.0) 12 (1.0) 59 (4.9) 1
164 (25.2) 193 (29.7) 293 (45.1) 12 194 (29.4) 81 (12.3)
155 (29.6) 178 (34.0) 191 (36.5) 30 46 (8.3) 28 (5.1)
319 (27.2) 371 (31.6) 484 (41.2) 42 240 (19.8) 109 (9.0)
81 (12.2) 216 (32.6) 125 (18.9) 70 (10.6) 62 (9.4) 56 (8.5) 52 (7.9) 190 (28.7) 284 (43.0) 20 (3.0) 272 (41.3)
130 (23.5) 161 (29.1) 117 (21.1) 67 (12.1) 54 (9.7) 11 (2.0) 14 (2.5) 149 (27.3) 173 (32.1) 23 (4.2) 183 (34.0)
211 (17.4) 377 (31.0) 242 (19.9) 137 (11.3) 116 (9.5) 67 (5.5) 66 (5.4) 339 (28.1) 457 (38.1) 43 (3.6) 455 (38.0)
0 (0.0) 4 (0.6) 397 (60.1) 257 (38.9) 3 (0.5) 1
86 (15.6) 71 (12.9) 302 (54.7) 92 (16.7) 1 (0.2) 2
86 (7.1) 75 (6.2) 699 (57.6) 349 (28.8) 4 (0.3) 3
0.0115†
<.0001† <.0001† <.0001†
0.6005† <.0001† 0.2673† 0.0101† <.0001†
<.0001† 552 (83.4) 110 (16.6)
285 (51.5) 268 (48.5)
837 (68.9) 378 (31.1)
Missing, n ER+, n (%) PR+, n (%) HER2+, n (%) Triple negative, n (%) * t-test †Chi-square test RT, radiation therapy
0 464 (70.1) 384 (58.0) 112 (16.9) 126 (19.0)
1 429 (77.4) 366 (66.1) 119 (21.5) 78 (14.1)
1 893 (73.4) 750 (61.7) 231 (19.0) 204 (16.8)
0.0039† 0.0040† 0.0434† 0.0213†
S1072-7515(20)30114-9
DOI:
https://doi.org/10.1016/j.jamcollsurg.2020.01.006
Reference:
ACS 9723
To appear in:
Journal of the American College of Surgeons
Received Date: 11 December 2019
Please cite this article as: Shammas RL, Broadwater G, Cason RW, Glener AD, Sergesketter AR, Vernon R, Le E, Wickenheisser T, Marks C, Hollenbeck ST, Assessing the Utility of Post-Mastectomy Imaging after Breast Reconstruction, Journal of the American College of Surgeons (2020), doi: https:// doi.org/10.1016/j.jamcollsurg.2020.01.006. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons.
Assessing the Utility of Post-Mastectomy Imaging after Breast Reconstruction Ronnie L Shammas, MD1, Gloria Broadwater, MS2, Roger W Cason, MD1, Adam D Glener, MD1, Amanda R Sergesketter, MD1, Rebecca Vernon, BS1, Eliot Le, BS1, Tori Wickenheisser, BS1, Caitlin Marks, BS1, Scott T Hollenbeck, MD, FACS1 1
Division of Plastic, Maxillofacial, and Oral Surgery, Department of Surgery, Duke University Health System, Durham, NC 2 Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University Medical Center, Durham, NC Disclosure Information: Nothing to disclose. Presented at the Southern Surgical Association 131th Annual Meeting, Hot Springs, VA, December 2019.
Corresponding Author Contact Information: Scott T Hollenbeck, MD Associate Professor, Division of Plastic and Reconstructive Surgery Duke University Medical Center Box 3945 Durham, NC 27710, USA Phone: (919) 681-5079 | Fax: (919) 681-2670 Email: [email protected]
Brief Title: Post-Mastectomy Imaging and Breast Reconstruction
1
BACKGROUND: Few guidelines exist regarding surveillance and diagnostic imaging after breast reconstruction. This study investigates the influence of breast reconstruction on the frequency of post-mastectomy imaging, the relative utility of imaging, and its effect on overall and locoregional recurrence-free survival. STUDY-DESIGN: A retrospective review identified breast cancer patients (n=1216) who underwent mastectomy with or without reconstruction. Logistic regression identified surgical and oncologic predictors of post-reconstruction imaging. Kaplan-Meier methods determined the impact of post-reconstruction imaging on overall and locoregional recurrence-free survival. RESULTS: Overall, 662 (54.4%) patients underwent mastectomy only and 554 (45.6%) underwent breast reconstruction. Patients undergoing reconstruction were more likely to receive imaging compared to patients undergoing mastectomy only (n=205, 37.0% vs. n=168, 25.4%; p<.0001); however, this difference was not statistically significant after adjusting for age and follow-up time (p=0.16). Most radiographic studies were BI-RADS 1 (n=58, 30%) or 2 (n=95, 49%) and were ordered by non-surgical providers (n=128, 63%). Post-reconstruction imaging did not influence overall or locoregional recurrence-free survival. The 5-year survival probability for breast reconstruction patients who underwent imaging for a palpable mass, surveillance, or who did not undergo imaging was 100%, 95% (95% CI:89-100%), and 96% (95% CI: 94-99%), respectively. Post-reconstruction imaging was not a significant predictor of overall survival (HR, 0.95; 95% CI 0.61-1.46; p=0.30) CONCLUSION: The limited utility of routine post-reconstruction imaging should be reinforced when evaluating breast reconstruction patients. Multidisciplinary collaboration should be emphasized when attempting to distinguish benign post-surgical findings from a malignant process to reduce unnecessary imaging and biopsies following breast reconstruction.
2
INTRODUCTION Breast cancer remains one of the most common malignancies worldwide,1 with mastectomy rates continuing to rise.2 This has been paralleled by an increase in both autologous and implant-based breast reconstruction.3 Currently, the National Comprehensive Cancer Network (NCCN) recommends against the routine imaging of breast cancer patients who have had a mastectomy with or without breast reconstruction.4 Despite this, there remains no consensus amongst surgeons, oncologists, and radiologists regarding routine or diagnostic imaging in breast reconstruction patients. The incidence of locoregional recurrence after mastectomy has been reported to be between 1% and 10%5-8, with most recurrences occurring within 5 years of mastectomy. Historically, physical exam was the ideal method for detecting locoregional recurrence. However, recent advancements in breast reconstruction, such as pre-pectoral implant placement, have introduced concern about the effects of prosthetic or autologous breast reconstruction on the detection of superficial or chest wall recurrences. Despite previous studies that have reported on the limited utility of surveillance or diagnostic imaging following autologous breast reconstruction, there remains no consensus amongst providers regarding the appropriate use of post-mastectomy imaging in the reconstructed patient.7, 9, 10 Furthermore, the potential for breast reconstruction to impair the utility of physical exam to detect locoregional recurrences, in addition to the increased incidence of benign physical exam findings such as cystic lesions and fat necrosis, may lower the threshold for imaging after mastectomy.11 The goal of this study was to examine the influence of implant or autologous breast reconstruction on post-mastectomy imaging, and the utility of diagnostic or surveillance imaging following breast reconstruction. We hypothesized that a large proportion of breast reconstruction
3
patients would be imaged following mastectomy and that imaging would not confer an improvement in overall or locoregional recurrence-free survival. METHODS Study Design A retrospective review was performed on all adult female patients who were diagnosed with breast cancer and underwent mastectomy with or without breast reconstruction from 20102018 at Duke University Medical Center. Patients were categorized into two study groups: 1) Those who underwent mastectomy without breast reconstruction and 2) Those who underwent mastectomy with implant or autologous breast reconstruction. Exclusion criteria included patients who underwent a partial mastectomy or lumpectomy, combined autologous and implant reconstruction, those with incomplete or missing information from the patient record, and patients who had an initial diagnosis of stage IV cancer. In addition, patients were excluded if they did not carry a cancer diagnosis. A CONSORT diagram displaying study selection criteria is shown in Figure 1. Definition of Variables Independent variables analyzed in this study included age at mastectomy, follow-up time, race, ethnicity, BMI, diabetes, smoking status, cancer stage, TNM stage, chemotherapy type (adjuvant, neoadjuvant, no chemotherapy), radiation type (adjuvant, neoadjuvant, or no radiation), type of mastectomy, surgical laterality, hormone receptor status, human epidermal growth factor receptor-2 status (HER-2), BRCA status, the presence of locoregional recurrence, and overall survival. Specific reconstructive variables analyzed included timing of reconstruction (immediate or delayed), type of breast reconstruction (implant or autologous), and the use of fat grafting. With respect to radiographic variables, three forms of imaging were analyzed. These
4
included ultrasound, magnetic resonance imaging (MRI), and mammography. Specific radiographic variables included the total number of post-mastectomy imaging events, Breast Imaging Reporting and Data System (BI-RADS) scores, indication for imaging (surveillance or palpable mass on clinical exam), number of biopsies, radiologic interpretations of imaging, pathologic interpretations, and provider who ordered the imaging. Briefly, BI-RADS scores of 1 are considered negative, 2 are benign, 3 are probably benign, 4 are suspicious, 5 are highly suggestive of malignancy, and 6 are assigned to lesions of known biopsy-proven malignancy.12 Providers were categorized into five categories: primary care provider (PCP), breast surgeon, breast oncologist, plastic surgeon, or other. Locoregional recurrence was defined as that which occurred within the skin or chest wall of the breast. Patients who developed distant metastasis following mastectomy were not considered to have locoregional recurrence. Study Outcomes The primary endpoint for this study was receipt of imaging following mastectomy. Imaging tests in the form of MRI, ultrasonography, or mammography, that were performed on the post-mastectomy breast were considered an imaging event. In the instance of unilateral breast cancer, imaging of the intact, non-cancerous breast was not considered in the analysis. Secondary endpoints included overall and locoregional recurrence-free survival from the date of mastectomy. Statistical Analysis Categorical variables and proportions were compared using chi-square tests. T-tests and Wilcoxon rank sum tests compared continuous factors depending on the distribution of the data, and logistic regression models predicted receipt of imaging. Kaplan-Meier methods were used to estimate time to locoregional recurrence and time to death. Cox proportional hazards regression
5
was used to adjust for covariates while testing the predictability of post-reconstruction imaging on overall survival. P-values <0.05 were considered statistically significant. Analyses were conducted using SAS software (V 9.4; SAS Institute Inc., Cary, NC). Graphs were produced by R software (R Foundation for Statistical Computing, Vienna, Austria). RESULTS Patient population A total of 1,216 patients were analyzed after all exclusions. Of these 662 (54.4%) patients underwent mastectomy only and 554 (45.6%) underwent mastectomy with breast reconstruction. Of those undergoing breast reconstruction, 315 (56.9%) underwent autologous reconstruction and 239 (43.1%) underwent implant reconstruction. The baseline unadjusted characteristics of all patients categorized by those who did and did not undergo breast reconstruction are shown in eTable 1. Overall, the mean age of the study cohort was 57.4 (SD ± 13.39) years. Patients who underwent breast reconstruction were predominately of White race, younger, had fewer medical comorbidities, and had positive hormone receptor (ER/PR) and HER-2 receptor status cancers. The baseline characteristics of all patients who underwent breast reconstruction, categorized by reconstruction type (implant based or autologous), are shown in Table 1. Patients who underwent autologous breast reconstruction tended to have a higher BMI, were more likely to undergo delayed reconstruction, receive neoadjuvant chemotherapy and adjuvant radiation therapy, and undergo fat grafting. Association of Breast Reconstruction and Post-Mastectomy Imaging A total of 373 patients (30.7%) underwent a form of post-mastectomy imaging. On univariate analysis, patients who underwent autologous or implant-based breast reconstruction (n=205, 37.0%) underwent post-mastectomy imaging more frequently than mastectomy only
6
patients (n=168, 25.4%) (p<.0001). Given these observed differences, we then assessed which oncologic and surgical factors may predispose breast reconstruction patients to imaging following mastectomy. As shown in Table 2, univariate logistic regression revealed that younger age at mastectomy (OR, 0.68; 95% CI 0.56-0.82; p<.0001), longer follow-up time (OR, 6.50; 95% CI 3.14-13.45; p<.0001), palpable mass (p<.0001), and fat grafting (OR, 0.66; 95% CI 0.46-0.97) were significantly associated with an increased likelihood for post-mastectomy imaging. Notably, reconstruction type (autologous vs. implant), tumor stage, and the receipt of chemotherapy or radiation therapy were not predictive of post-mastectomy imaging. Multivariate logistic regression analysis indicated that after adjustment for covariates, only a younger age at mastectomy (OR, 0.75; 95% CI 0.59-0.967; p=0.026), increased length of follow up (OR, 6.72; 95% CI 2.75-16.41; p<.0001) and palpable mass (p<.0001) were independently predictive of imaging following mastectomy. Characteristics of Post-Mastectomy Imaging Following Breast Reconstruction The overall characteristics of the post-reconstruction imaging events are shown in Table 3. Given the relatively high incidence of post-reconstruction imaging, radiologic and pathologic interpretations of imaging and biopsies were analyzed to determine the relative utility of diagnostic or surveillance imaging in the reconstructed patient. Of the 205 reconstructed patients imaged, 119 received autologous reconstruction and 86 had implant-based reconstruction. Breast reconstruction patients received a total of 398 imaging events. Of these, autologous reconstruction patients underwent 262 (median 2.0) imaging events compared to 136 (median 1.0) in implant-based reconstruction (p=0.004). With respect to imaging modality, most breast reconstruction patients underwent a combination of mammogram and ultrasound. There was no significant difference in the frequency of post-mastectomy imaging for indications of
7
surveillance or for the evaluation of a palpable mass (n=95, 47.5% vs. n=105, 52.5%; p=0.98). When assessing which provider ordered the imaging study, most were ordered by the breast oncologist (n=128, 62.7%), while a minority were ordered by the breast surgeon (n=37, 18.1%) or plastic surgeon (n=8, 3.9%). Most imaging studies performed on breast reconstruction patients were considered “negative” or “benign” and received a BI-RADS score of 1 (n=58, 29.9%) or 2 (n=95, 49.0%). A total of 28 studies (14.4%) were interpreted as suspicious and were assigned a BI-RADS score of 4. Forty-seven patients (22.9%) underwent biopsies, with a total of 52 biopsies performed amongst breast reconstruction patients. There was no significant difference in the number of patients in which biopsies were performed when comparing autologous or implant-based reconstruction (n=27, 22.7% vs. n=20, 23.3%; p=0.92). With respect to radiologic and pathologic interpretations of imaging and biopsies, most findings were interpreted as benign post-surgical changes (n=103, 50.5%) or fat necrosis (n=33, 16.2%). In addition, patients who underwent autologous breast reconstruction more frequently had evidence of fat necrosis on imaging or biopsy. Out of a total of 9 locoregional recurrences that were detected amongst breast reconstruction patients, 5 were detected by imaging or biopsy. The remaining 4 were detected by physical exam and confirmed on pathology with surgical excision. Impact of Imaging After Breast Reconstruction on Overall and Locoregional Recurrence-Free Survival Kaplan-Meier curves were used to estimate the overall survival rates of breast reconstruction patients for those who did and did not undergo post-mastectomy imaging for indications of surveillance or the finding of a palpable mass on exam. Figure 2A represents the comparison of overall survival, and Figure 2B represents the comparison of locoregional
8
recurrence-free survival between breast reconstruction patients who underwent post-mastectomy imaging for a palpable mass or surveillance, and those who did not undergo imaging. Breast reconstruction patients who underwent imaging for surveillance, or for a palpable mass, displayed no clinically meaningful difference in overall survival as compared to breast reconstruction patients who did not undergo imaging. In addition, there was no clinically meaningful difference in locoregional recurrence-free survival when comparing patients who did or did not undergo imaging for indications of surveillance or the detection of a palpable mass. The overall 5-year survival probability for breast reconstruction patients who underwent imaging for indications of a palpable mass or surveillance, and those who did not undergo imaging was 100%, 95% (95% CI: 89-100%), and 96% (95% CI: 94-99%), respectively. Among those who received imaging for indications of a palpable mass or surveillance, and those who did not receive post-mastectomy imaging, the 5-year locoregional recurrence-free probability was 95% (95% CI: 90-99%), 99% (95% CI: 97-100%), and 99% (95% CI: 97-100%), respectively. A Cox proportional hazard model was used to assess the effect of post-mastectomy imaging on overall survival amongst breast reconstruction patients. After adjusting for age at mastectomy and follow-up time, post-mastectomy imaging was not found to be a significant predictor of overall survival (HR, 0.95; 95% CI 0.61-1.46; p=0.30). DISCUSSION In this retrospective review, a noteworthy proportion of breast reconstruction patients underwent imaging or biopsy following mastectomy. Furthermore, younger patients were more likely to undergo imaging after breast reconstruction, despite most imaging and biopsies resulting in a benign finding. When assessing the impact of post-mastectomy imaging on
9
survival, imaging in the reconstructed patient for indications of surveillance or a palpable mass did not affect overall or locoregional recurrence-free survival. While the rates of post-mastectomy breast reconstruction continue to rise, there remains no consensus regarding the use of routine or diagnostic breast imaging in the reconstructed patient.13, 14 Currently, the gold standard for monitoring the development of locoregional recurrence is physical examination. However, advanced reconstructive techniques that cover the chest wall and result in the appearance of a near normal-appearing breast, have resulted in increased uncertainty amongst providers regarding the need for surveillance imaging. Furthermore, the increased incidence of benign physical exam findings, such as oil cysts and fat necrosis, may increase the frequency of post-mastectomy imaging and biopsy in the reconstructed patient. Our findings suggest that post-mastectomy imaging for indications of routine surveillance has limited utility, and that imaging for indications of surveillance or the detection of a palpable mass have limited effect on overall or locoregional-recurrence free survival following breast reconstruction. Increased emphasis should be placed on physical examination as a surveillance strategy, and multidisciplinary communication should be emphasized to better define the likelihood of a benign physical exam finding due to reconstructive techniques and reduce the incidence of unnecessary imaging and biopsy after mastectomy. The overwhelming consensus amongst providers is that there is little utility in surveillance imaging to detect locoregional recurrence after mastectomy.15, 16 However, no such consensus exists for patients undergoing breast reconstruction. Initial concerns that breast reconstruction may impede the detection of locoregional recurrence, or stimulate dormant disease with the transfer of autologous tissue have remained unfounded.17, 18 Reddy et al.
10
reported that the incidence and time to detection of locoregional recurrence did not differ in patients who did or did not undergo reconstruction.17 Furthermore, when examining the role of surveillance imaging in a seemingly normal appearing breast following implant or autologous breast reconstruction, Zakhireh et al. emphasized that there is insufficient evidence to recommend annual mammograms over physical examination for the detection of locoregional recurrence.5-7, 9, 10, 19 In a study by Noroozian et al., which reviewed 515 patients who had undergone autologous breast reconstruction and mammographic surveillance, the oncologic safety of breast reconstruction was re-demonstrated with locoregional recurrence reported as 3.9% (20 of 515 women). While mammogram did aid in the detection of clinically occult disease, the majority of locoregional recurrences could be detected with physical examination.19 Despite previously published work demonstrating the limited utility of mammography following breast reconstruction, our study demonstrates that a large proportion of breast reconstruction patients are subject to frequent imaging in the form of ultrasonography, mammography, or MRI, with a large proportion of these patients still undergoing imaging for the purposes of cancer surveillance. The rate of locoregional recurrence reported in this study (1.6%) following breast reconstruction is consistent with prior reports17 and reinforces the oncologic safety of reconstructive techniques. With respect to radiologic findings and pathologic interpretations following biopsy, most suspected abnormalities were determined to be benign lesions. Often, these were classified as normal post-surgical changes or fat necrosis. Palpable lumps after fat grafting due to fat necrosis are known to be a common occurrence following breast reconstruction.20 Consequently, as reconstructive techniques advance and the use of fat grafting continues to increase,21 defining the optimum surveillance strategy for the associated palpable abnormalities has become increasingly important. Based on our results, we suggest that
11
palpable masses in the reconstructed population who have recently undergone fat grafting may be conservatively managed with surveillance via physical examination. The workup of a post-reconstructive breast lesion should be considered in a multidisciplinary setting. Prior studies have shown that knowledge deficits and differences in goals of care exist between medical oncology and plastic surgery when considering complications and diagnostic workups.22 The results of our study found that within the authors’ institution, most imaging studies in the reconstructed patient were ordered by the medical oncology team, while a minority tended to be ordered by the breast surgeon and/or plastic surgeon. This may be partially attributed to a lack of appropriate communication amongst providers when attempting to distinguish expected physical exam findings following breast reconstruction (i.e. fat necrosis) from a malignant process. Furthermore, as emphasized in this study and others, the use of imaging for indications of surveillance, or for the evaluation of a palpable mass, does not improve overall survival or locoregional recurrence-free survival when compared to breast reconstruction patients who do not undergo imaging.9, 10, 17-19 The limited utility of routine imaging should be emphasized in the evaluation of a breast reconstruction patient; and improved multidisciplinary communication should be implemented when attempting to distinguish benign post-surgical findings from a malignant processes in order to reduce unnecessary imaging and biopsies following breast reconstruction. Study Limitations This study is limited by its retrospective design. Similar to other studies, patients who underwent mastectomy without reconstruction tended to represent an older population of women with more aggressive tumor types and treatment courses, and shorter lengths of follow-up and overall survival.10, 17 In addition, while the rates of locoregional recurrence in this study are
12
similar to those previously reported,17 the low number precludes any meaningful statistical conclusions that can be drawn when comparing patients who did and did not undergo reconstruction and developed a locoregional recurrence. Although this study represents the largest cohort of cancer patients who did and did not undergo breast reconstruction, a multiinstitutional study is needed to make an adequate statistical comparison of patients when considering the development of locoregional recurrence. However, the focus of this study was not to evaluate locoregional recurrence, but rather to examine the relative utility of imaging in breast reconstruction patients. CONCLUSION To date, there remains no standardized consensus regarding the appropriate surveillance strategy for recurrence in the reconstructed patient. Our study revealed that overall, breast reconstruction patients are more frequently imaged following mastectomy, and younger age is independently predictive of post-mastectomy imaging. Most radiologic and pathological results were reported as benign findings, and most studies were not ordered by the surgical team. Furthermore, post-mastectomy imaging in the breast reconstruction patient for indications of a palpable mass or for surveillance did not affect overall survival or disease-free survival. Overall, these findings emphasize the need for improved communication across subspecialties to minimize the incidence of unnecessary imaging and biopsy in the reconstructed patient. Future prospective studies are needed to further define the role of mammography and ultrasound following breast reconstruction to determine the benefits of imaging on oncologic outcomes.
13
Précis Breast reconstruction patients undergo post-mastectomy imaging more frequently than mastectomy only patients. Post-reconstruction imaging for indications of a palpable mass or surveillance did not affect overall or disease-free survival. Improved multidisciplinary communication is needed to minimize the incidence of unnecessary imaging and biopsy in the reconstructed patient.
14
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Lin JY, Song P, Pu LLQ. Management of fat necrosis after autologous fat transplantation
for breast augmentation. Plast Reconstr Surg 2018;142:665e-673e. 21.
Hollenbeck ST, Hwang ES. Fat grafting-more than just the hype. JAMA Surg
2017;152:951-952. 22.
Milucky JL, Deal AM, Anders C, et al. Coordination of care for breast reconstruction
patients: A provider survey. Clin Breast Cancer 2017;17:e59-e64.
17
Table 1. Patient Characteristics for Reconstructed Subset by Type of Reconstruction
Variable Age at oncologic mastectomy, y, mean (SD) Follow-up, y, mean (SD) Race/ethnicity, n (%) White African American Hispanic/Latino Other or unspecified Missing, n BMI at mastectomy, n (%) <25 kg/m2 25-30 kg/m2 >30 kg/m2 Missing, n Diabetes, n (%) Smoker, n (%) Tumor stage, n (%) 0 I IIA IIB IIIA IIIB IIIC Neoadjuvant chemotherapy, n (%) Adjuvant chemotherapy, n (%) Neoadjuvant RT, n (%) Adjuvant RT, n (%) Mastectomy type, n (%) Nipple sparing Skin sparing Simple Modified radical Radical Missing, n Mastectomy laterality, n (%) Unilateral Bilateral Missing, n Reconstruction timing, n (%) Immediate
Type of reconstruction performed? Autologous Implant-based (n=316) (n=241) 50.0 (8.57) 50.3 (11.01)
Total (n=557)
p Value
50.1 (9.69)
0.6707* 0.7117* 0.4959†
4.0 (2.63)
4.0 (2.54)
4.0 (2.59)
235 (74.6) 60 (19.0) 2 (0.6) 18 (5.7) 0
177 (74.4) 43 (18.1) 5 (2.1) 13 (5.5) 1
412 (74.5) 103 (18.6) 7 (1.3) 31 (5.6) 1 <.0001†
65 (21.3) 113 (37.0) 127 (41.6) 10 29 (9.2) 20 (6.3)
90 (41.1) 65 (29.7) 64 (29.2) 20 17 (7.1) 8 (3.3)
155 (29.6) 178 (34.0) 191 (36.5) 30 46 (8.3) 28 (5.1)
72 (22.9) 82 (26.0) 59 (18.7) 43 (13.7) 39 (12.4) 8 (2.5) 12 (3.8) 108 (35.0) 93 (30.4) 21 (6.8) 132 (43.4)
58 (24.3) 79 (33.1) 58 (24.3) 24 (10.0) 15 (6.3) 3 (1.3) 2 (0.8) 41 (17.4) 80 (34.3) 2 (0.9) 51 (21.8)
130 (23.5) 161 (29.1) 117 (21.1) 67 (12.1) 54 (9.7) 11 (2.0) 14 (2.5) 149 (27.3) 173 (32.1) 23 (4.2) 183 (34.0)
27 (8.6) 40 (12.8) 170 (54.3) 75 (24.0) 1 (0.3) 2
59 (24.7) 31 (13.0) 132 (55.2) 17 (7.1) 0 (0.0) 0
86 (15.6) 71 (12.9) 302 (54.7) 92 (16.7) 1 (0.2) 2
187 (59.6) 127 (40.4) 1
98 (41.0) 141 (59.0) 0
285 (51.5) 268 (48.5) 1
108 (34.4)
193 (81.1)
301 (54.5)
0.3765† 0.1102† 0.0095†
<.0001† 0.3314† 0.0006† <.0001† <.0001†
<.0001†
<.0001†
18
Delayed Missing, n ER+, n (%) PR+, n (%) HER2+, n (%) Triple negative, n (%) Fat grafting, n (%) Breast imaging after mastectomy, n (%)
206 (65.6) 1 237 (75.2) 208 (66.0) 68 (21.6) 48 (15.2) 119 (37.9) 119 (37.8)
45 (18.9) 1 192 (80.3) 158 (66.1) 51 (21.3) 30 (12.6) 43 (18.3) 86 (36.0)
251 (45.5) 2 429 (77.4) 366 (66.1) 119 (21.5) 78 (14.1) 162 (29.5) 205 (37.0)
0.1552† 0.9849† 0.9438† 0.3680† <.0001† 0.6648†
*
t-test †Chi-Square test; RT, radiation therapy
19
Variable, comparison
Odds ratio
Lower confidence limit
Upper confidence limit
Age at mastectomy 10-year increase
<.0001 0.680
0.564
0.819
Reconstruction type Autologous vs implant
0.665 1.080
0.762
1.531
Race
0.244
White vs African American
1.268
0.815
1.972
White vs Hispanic
0.737
0.141
3.844
White vs other
1.964
0.944
4.087
Diabetes Yes vs no
0.994 1.002
0.536
1.873
Smoker Yes vs no
0.797 0.903
0.414
1.968
Tumor stage
0.118
Stage 3 vs 0
0.640
0.355
1.153
Stage 3 vs 1
1.161
0.671
2.011
Stage 3 vs 2
0.887
0.516
1.525
Neoadjuvant chemotherapy Yes vs no
0.342 0.829
0.563
1.220
Adjuvant chemotherapy Yes vs no
0.824 0.959
0.660
1.392
Neoadjuvant radiation Yes vs no
0.487 1.378
0.557
3.410
Adjuvant radiation Yes vs no
0.808 0.955
0.661
1.380
BMI category
0.144
25-30 kg/m2 vs < 25 kg/m2
1.122
0.724
1.740
> 30 kg/m2 vs < 25 kg/m2
0.741
0.476
1.153
Laterality of reconstruction Unilateral vs bilateral Years of follow-up
p Value
0.496 0.887
0.627
1.253 <.0001
20
10-year increase
6.495
3.137
13.445
Fat grafting Yes vs no
0.032 0.663
0.456
0.965
Reconstruction timing Immediate vs delayed
0.269 1.216
0.860
1.720
Palpable mass* Yes vs no
<.0001 NA
NA
NA
BRCA status Positive vs negative
0.310 0.752
0.433
1.304
*OR not estimable due to few patients with a palpable mass not imaged NA, not applicable
21
Table 3. Characteristics of Breast Reconstruction Patients Who Underwent Post-Mastectomy Imaging Variable No. of post-mastectomy imaging events Total, n Median (range) Imaging type, n (%) Ultrasound only MRI only Mammogram only > 1 type BI-RADS, n (%) 1 2 3 4 Missing, n Indication for imaging, n (%) Surveillance Palpable mass on exam Missing, n Biopsy performed, n (%) Total no. of biopsies performed to date Total, n Median (range) If a mass was palpated, which occurred? n (%) Imaging followed by biopsy Direct to biopsy Imaging only Radiologic and pathologic interpretation of imaging and biopsy, n (%) Normal Recurrence Fat necrosis Other Multiple Missing Provider who ordered imaging/biopsy, n (%) Primary care provider Breast surgeon Breast oncologist Plastic surgeon Other Multiple
Type of reconstruction performed? Autologous Implant-based (n=119) (n=86)
Total (n=205)
p Value 0.00352
262 2.0 (1.0, 10.0)
136 1.0 (1.0, 5.0)
398 2.0 (1.0, 10.0) 0.25371
20 (16.8) 17 (14.3) 24 (20.2) 58 (48.7)
23 (26.7) 15 (17.4) 15 (17.4) 33 (38.4)
43 (21.0) 32 (15.6) 39 (19.0) 91 (44.4) 0.81621
34 (30.4) 52 (46.4) 8 (7.1) 18 (16.1) 7
24 (29.3) 43 (52.4) 5 (6.1) 10 (12.2) 4
58 (29.9) 95 (49.0) 13 (6.7) 28 (14.4) 11 0.97711
55 (47.4) 61 (52.6) 3 27 (22.7)
40 (47.6) 44 (52.4) 2 20 (23.3)
95 (47.5) 105 (52.5) 5 47 (22.9)
30 1.0 (1.0, 2.0)
22 1.0 (1.0, 2.0)
52 1.0 (1.0, 2.0)
0.92411 0.90382
0.40811 30 (25.2) 1 (0.8) 88 (73.9)
22 (25.5) 2 (2.3) 62 (72.1)
52 (25.3) 3 (1.4) 150 (73.2) 0.04691
51 (42.9) 4 (3.4) 24 (20.2) 17 (14.3) 23 (19.3) 0
52 (61.2) 1 (1.2) 9 (10.6) 14 (16.5) 9 (10.6) 1
103 (50.5) 5 (2.5) 33 (16.2) 31 (15.2) 32 (15.7) 1 0.74671
5 (4.2) 19 (16.1) 77 (65.3) 4 (3.4) 2 (1.7) 11 (9.3)
6 (7.0) 18 (20.9) 51 (59.3) 4 (4.7) 2 (2.3) 5 (5.8)
11 (5.4) 37 (18.1) 128 (62.7) 8 (3.9) 4 (2.0) 16 (7.8)
22
Missing, n
1
0
1
*Chi-square test †Wilcoxon rank-sum test BI-RADS, Breast Imaging Reporting and Data System
23
Figure Legends: Figure 1: CONSORT diagram of patient selection criteria. Figure 2: Kaplan-Meier probability for (A) overall survival and (B) locoregional recurrence-free survival for reconstruction subset.
24
Precis Breast reconstruction patients undergo imaging more frequently than mastectomy only patients. Post-reconstruction imaging for indication of a palpable mass or surveillance did not affect overall or disease-free survival. Improved multidisciplinary communication is needed to minimize unnecessary imaging and biopsy in the reconstructed patient.
25
eTable 1. Patient Characteristics
Variable
Age at oncologic mastectomy, y, mean (SD) Follow up, y, mean (SD) Race/ethnicity, n (%) White African American Hispanic/Latino Other or unspecified Missing, n BMI at mastectomy, n (%) <25 kg/m2 25-30 kg/m2 >30 kg/m2 Missing, n Diabetes, n (%) Smoker, n (%) Tumor stage, n (%) 0 I IIA IIB IIIA IIIB IIIC Neoadjuvant chemotherapy, n (%) Adjuvant chemotherapy, n (%) Neoadjuvant RT, n (%) Adjuvant RT, n (%) Type of mastectomy, n (%) Nipple sparing Skin sparing Simple Modified radical Radical Missing, n Mastectomy laterality, n (%) Unilateral Bilateral
Did the patient undergo reconstruction after mastectomy? No Yes (n=662) (n=554)
Total (n=1216)
p Value
63.5 (13.01)
50.1 (9.69)
57.4 (13.39)
<.0001*
4.0 (2.88)
4.0 (2.59)
4.0 (2.75)
0.8066* <.0001†
404 (61.0) 225 (34.0) 5 (0.8) 28 (4.2) 0
412 (74.5) 103 (18.6) 7 (1.3) 31 (5.6) 1
816 (67.2) 328 (27.0) 12 (1.0) 59 (4.9) 1
164 (25.2) 193 (29.7) 293 (45.1) 12 194 (29.4) 81 (12.3)
155 (29.6) 178 (34.0) 191 (36.5) 30 46 (8.3) 28 (5.1)
319 (27.2) 371 (31.6) 484 (41.2) 42 240 (19.8) 109 (9.0)
81 (12.2) 216 (32.6) 125 (18.9) 70 (10.6) 62 (9.4) 56 (8.5) 52 (7.9) 190 (28.7) 284 (43.0) 20 (3.0) 272 (41.3)
130 (23.5) 161 (29.1) 117 (21.1) 67 (12.1) 54 (9.7) 11 (2.0) 14 (2.5) 149 (27.3) 173 (32.1) 23 (4.2) 183 (34.0)
211 (17.4) 377 (31.0) 242 (19.9) 137 (11.3) 116 (9.5) 67 (5.5) 66 (5.4) 339 (28.1) 457 (38.1) 43 (3.6) 455 (38.0)
0 (0.0) 4 (0.6) 397 (60.1) 257 (38.9) 3 (0.5) 1
86 (15.6) 71 (12.9) 302 (54.7) 92 (16.7) 1 (0.2) 2
86 (7.1) 75 (6.2) 699 (57.6) 349 (28.8) 4 (0.3) 3
0.0115†
<.0001† <.0001† <.0001†
0.6005† <.0001† 0.2673† 0.0101† <.0001†
<.0001† 552 (83.4) 110 (16.6)
285 (51.5) 268 (48.5)
837 (68.9) 378 (31.1)
Missing, n ER+, n (%) PR+, n (%) HER2+, n (%) Triple negative, n (%) * t-test †Chi-square test RT, radiation therapy
0 464 (70.1) 384 (58.0) 112 (16.9) 126 (19.0)
1 429 (77.4) 366 (66.1) 119 (21.5) 78 (14.1)
1 893 (73.4) 750 (61.7) 231 (19.0) 204 (16.8)
0.0039† 0.0040† 0.0434† 0.0213†