- Email: [email protected]
Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer
European Journal of Surgical Oncology xxx (xxxx) xxx
Contents lists available at ScienceDirect
European Journal of Surgical Oncology journal homepage: www.ejso.com
Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer F. De Lorenzi a, *, 1, G. Corso b, c, 1, F. Botta d, A. Invento b, A. Marchetti a, P. Sala a, G. Vottero a, V. Bagnardi d, C. Leonardi e, P. Veronesi b, c, A. Goldhirsch f a
Division of Plastic and Reconstructive Surgery, European Institute of Oncology IRCCS, Milan, Italy Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy Department of Oncology and Hemato-Oncology, University of Milan, Italy d Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy e Division of Radiation Oncology, European Institute of Oncology, IRCCS, Milan, Italy f Multimedica, Milan, Italy b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 8 November 2019 Received in revised form 17 December 2019 Accepted 8 January 2020 Available online xxx
Background: Ipsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed. Methods: We retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction. All included patients with IBTR previously underwent conserving surgery for BC, and received a postoperative irradiation. Primary endpoints were disease free survival and overall survival. Secondary endpoints were surgical complications and reinterventions. Results: Invasive ductal cancer was the most frequent histotype (60.4%) of breast cancer reappearance. rpT1, rpT2 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Post-operative complication other than seroma occurred in 17,1% of patients, while seroma at the donor site was observed in 61.3% of cases. At 5-year after surgery overall survival was 92% (95% CI: 85%e96%) and disease free survival was 78% (95% CI: 69%e85%). Conclusions: Immediate latissimus dorsi flap reconstruction in selected patients with isolated breast tumor recurrence, which occurred after breast irradiation, provides an effective treatment with a satisfactory outcome. © 2020 Published by Elsevier Ltd.
Keywords: Breast reconstruction Breast relapse Breast cancer
Introduction About 7% of patients with primary breast cancer (BC) develop a loco-regional recurrence after primary cancer treatment, independently of surgical approach [1]. Locoregional recurrence is described as ipsilateral, in-breast tumor recurrence after lumpectomy (IBTR), chest wall recurrence after mastectomy, or recurrence in the ipsilateral axillary or supraclavicular lymph nodes (less commonly infraclavicular and/or internal mammary nodes). Since
* Corresponding author. Division of Plastic and Reconstructive Surgery, European Institute of Oncology IRCCS, via G. Ripamonti 435, Milan, 20141, Italy E-mail address: [email protected] (F. De Lorenzi). 1 Contributed equally.
the natural history of the disease is different in patients with either luminal disease, with HER2 overexpression, or with triple negative disease, such three different subpopulations can be identified. The different molecular subtypes reflect the biological diversity of breast cancer and they have proven to be a powerful predictor of survival and distant recurrence [2e4]. Because most first IBTRs are operable, management of the recurrence is aimed at control of local disease via surgical excision and selective use of radiation therapy, depending on prior treatments. Salvage mastectomy is the most common operation and latissimus dorsi (LD) flap is frequently used for breast reconstruction. Immediate reconstruction with LD flap for primary BCs has been largely described [5e9]. It has been demonstrated that it does not interfere with systemic adjuvant treatments and overall survival,
https://doi.org/10.1016/j.ejso.2020.01.015 0748-7983/© 2020 Published by Elsevier Ltd.
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
2
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
time to distant or local relapses [10]. It is considered a safe option for both invasive and in situ cancers, [11]. Only few data exist regarding the use of LD flap in patients with isolated local or loco regional recurrence of BC [12]. The aim of the study is to investigate the BC related events, or death and surgery-related complications after LD reconstructions in patients who had a local relapse (without identified systemic disease). Patients and methods Between 2002 and 2011, in the European Institute of Oncology (IEO) institutional data base we identified 111 consecutive patients who had an isolated local recurrence and who underwent immediate LD reconstruction. All patients who developed IBTR previously underwent conserving surgery for BC, followed by postoperative irradiation. Clinical and pathological data as age at cancer onset, body mass index (BMI), TNM classification, histotype and smoking status were recorded. Detected levels of ER, PgR, and HER2 overexpression and/or amplification (FISH test) and Ki-67 were used to define subsets of breast cancer molecular subtypes: Luminal Aelike tumors are ERpositive and HER2-negative with low Ki-67 expression (<14%) or with intermediate Ki-67 expression (14%e19%) and high PgR levels (20%); Luminal Belike tumors are ER-positive with intermediate Ki-67 expression (14%e19%) and low PgR levels (<20%) or with high Ki-67 expression (20%) or ER-positive and HER2-positive; Triple negative tumors are ER-, PgR- and HER2-negative and HER2 positive tumors are ER- and PgR-negative and HER2-positive [13]. Patients presenting bone and/or soft tissue (beyond regional lymph nodes) and/or visceral relapses as first event were excluded from the study group as well as patients who received exclusive electron intra-operative radiotherapy and/or intraoperative boost and external irradiation as primary irradiation. Objectives Primary endpoints were to assess disease free interval (DFI) and subsequent relapse (type and organ) and/or death in the entire cohort and according to BC subtypes [13] (i.e. luminal A, luminal B (Ki67 20%), luminal B (HER2 positive), HER2 positive-not luminal, and triple negative). Secondary endpoints were surgery-related complications and their potential influence on oncologic outcomes (minor complications not requiring further surgery; major complications requiring re-intervention). Previous radiotherapy Three-dimensional conformal radiotherapy was delivered to the whole breast with two opposed tangential fields of 6-MV photons or mixed energy 6e18 MV in case of large breast. A boost dose was always applied. The treatment schedule consisted of either conventional fractionation (50 Gy in 25 fractions followed by sequential boost of 10 Gy in 5 fractions with electrons) or moderate hypo fractionation (45 Gy in 20 fractions and concomitant boost of 5 Gy, delivered with photons or electrons). All patients underwent CT simulation and were treated in supine position with both the arms raised above the head. The clinical target volume (CTV) was delineated on the CT scan. The planning target volume was created by applying 1.5-cm margins to the CTV in craniocaudal directions and towards the air. The lateral border was at the midaxillary line. Regarding the posterior margin, care was taken not to exceed 2.5 cm for the central lung distance and 1 cm for the maximal heart
distance in left-sided breast. Multileaf collimator and optimized beam set-up were used to meet the dose -volume constraints for contralateral breast (no point receiving >15% of the prescribed dose, PD), heart (10% of the heart not exceeding 25 Gy, V25 10%), and ipsilateral lung (20% of the lung not exceeding 20 Gy, V20 20%). The treatment plans were normalized at the International Commission on Radiation Units and Measurements (ICRU) reference point. Wedge compensation was used to achieve a uniform dose distribution across the PTV (5% to þ7% of the PD) as recommended by ICRU report 50 [14]. Preoperative planning and design The function of the latissimus dorsi flap was clinically assessed; good function generally indicates that the thoracodorsal pedicle is intact. In case of any doubt (i.e. previous surgery and scars in the dorsal and axillary areas), ultrasound examination with Doppler of the axillary region was performed. The reconstruction was designed with the patient in a standing position. The dorsal skin paddle was marked according to natural folds of skin and fat in the dorsal region and according to incisions and skin removal at the mastectomy site. Therefore, flap design has been tailored to each patient. In all the patients, the amount of dorsal skin available was carefully assessed using the pinch test so that closure was performed entirely free from tension. Operative technique and positioning and modeling of the flap After mastectomy and axillary surgery were carried out, the patient was placed in a lateral position with the arm in abduction to open the axillary hollow. The identification of the thoracodorsal pedicle was assessed through the mastectomy or axillary skin incision. Afterwards, the dissection differed in case of autologous or latissimus dorsi flap and implant. In case of autologous pedicled transfer, the dorsal skin paddle was incised until the fascia superficialis and dissection followed the deep aspect of the fascia superficialis, taking in care to leave the deep fat on the muscle. Fatty areas in the scapular region, from the anterior margin of the latissimus dorsi and from the love handles were included within the flap as well as deep fat. In case of pedicled transfer and implant reconstruction, the dorsal skin paddle was incised directly to the fascia profunda, just above the muscle and dissection followed muscular fibers in any direction. The anterior margin of the latissimus dorsi was first identified, and when it was completely undermined the distal part was transacted. The dissection continued in the submuscular deep space, carefully ligating or coagulating the accessory pedicles. The pedicle, already identified anteriorly from the mastectomy/axillary incision, was approached posteriorly by releasing the teres major from the latissimus. The pedicle of the serratus anterior was generally followed up to the Y-bifurcation thoracodorsal vessels. In all patients the thoracodorsal nerve to the latissimus dorsi muscle was not divided. To make flap transposition easier and without tension, in some cases was necessary the partial proximal section of the tendon. The flap was transposed to the breast area via a subcutaneous tunnel. The donor site was closed after irrigation of the whole area in order to obtain perfect hemostasis. Quilting sutures were not always used. One or two suction drains were placed in the back. Positioning and modeling of the flap differed according to mastectomy scar and the necessity of replace part of the breast skin. If possible, original breast skin was preserved and the skin paddle almost totally de epithelialized, avowing patch effect of the dorsal skin.
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
A suction drain was inserted. Modeling differed in case of autologous reconstructions or with the use of implants. In both cases, the patient was put in a sitting position on the surgical table to check the shape and volume of the reconstructed breast. In case of implant and latissimus, sizers were used to choose the right implant. Follow up Following surgery, all patients were discussed during the weekly multidisciplinary meeting attended by plastic and breast dedicated surgeons, medical oncologists, radiation oncologists and pathologists. The decision for adjuvant systemic treatment was made on the basis of biological features, staging, previously received treatments and comorbidities, according to international approved guidelines regularly updated (St.Gallen) [15]. The clinical follow-up of the different subpopulations was similar and planned every six months. A radiological examination of the breasts was performed every year (including bilateral ultrasound and mammogram of the healthy breast) or more frequently in case of clinical suspicion. Implant integrity was checked annually with ultrasound, only in case of suspected rupture MRI was recommended. Liver and bone were checked every year as well as biological markers.
3
Breast reconstruction was performed with autologous LD in 17.1% of patients and in association with implant in 82.9% of cases. Post-operative complications Seroma formation in the donor area occurred in 68 out of 111 flaps (61.3%). They were all treated conservatively by aspiration at outpatient clinic. Excluding these seromas, which have not been considered a complication but an expected draw back of the technique, in total we observed postoperative complications in 17.1% of patients. The most frequent complications at the reconstructed breast were mastectomy skin flap necrosis (6.7%) and seroma formation (3,6%). Even seromas at the reconstructed breast were conservatively treated. The most frequent complication at the donor area of the flap was hematoma formation that occurred in 3,6% of patients. No significant difference was observed among the different molecular subtypes of cancer reappearance with regard to overall post-operative complications. Similarly, no specific complication was associated with any subgroup of patients (Table 2). Implant loss at the side of salvage mastectomy occurred in four patients (4,3%). In two patients it was due early necrosis of mastectomy flaps, in one case to wound dehiscence at the side of reconstruction and in one other patient the implant was removed due to further surgery for local relapse in the interval study.
Statistical analysis Oncologic outcomes A descriptive analysis was performed for patients' and tumors’ characteristics evaluated both at the time of primary and recurrence surgeries, and post-operative complications after reconstruction surgery due to recurrence. Continuous data were reported as median and interquartile range (IQR) and categorical data as counts ad percentages (%). Moreover, overall survival (OS) and disease-free survival (DFS) functions were estimated applying the Kaplan-Meier method and, in order to evaluate differences among BC subtypes, the log-rank test was performed. The cumulative incidence of locoregional recurrences was calculated using Kalbfleisch and Prentice method, with distant metastases, contralateral recurrences, other primaries and deaths as first observed event considered as competing events. A P-value<0.05 was considered statistically significant. All analyses were performed with the use of SAS software, version 9.4 (SAS Institute, Cary; NC).
Overall survival (OS) was respectively 92% (95% CI: 85%e96%) at 5-year and 82% (95% CI: 70%e89%) at 10-year after surgery in the all population (Fig. 1). Patients with biologically aggressive disease at diagnosis (Luminal B or HER 2 positive) had worse OS at 5 years than others (94% (95% CI: 63%e99%) (Fig. 2). The overall DFS was 78% (95% CI: 69%e85%) at 5 year (Fig. 3) and 63% (95% CI: 50%e73%) at 10 year. The 5- and 10-yr cumulative incidence of locoregional recurrences was, respectively, 7% (95% CI: 3%e13%) and 10% (95% CI: 5%e18%) (Fig. 4). Considering the different sub-groups, DFS at 5-year was 82% (95% CI: 45%e95%) in Luminal A group, compared with 71% (95% CI: 51%e83%) and 93% (95% CI: 59%e99%) in Luminal B group (Ki67 20%) and in Luminal B group (HER 2 positive), respectively (Fig. 5). Due to the low number of the stratified groups, DFS at 10-year was omitted.
Results Discussion Patients’ characteristics Patients’ characteristics are described in Table 1. The most frequent histotypes at primary were invasive ductal carcinoma (IDC) in 67.6% of patients and ductal carcinoma in situ in 15.3%. All patients presented positive axillary nodes at first onset. Luminal B (Ki67 20%) was the most frequent subtype identified (23.4%). Invasive ductal cancer was the most frequent histotype (60.4%) of BC reappearance. rpT1, rpT2 N0 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the all patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Luminal B (hormone receptor positive and Ki67 20%) was the most frequent subtype even among IBTRs (29.7%). Unfortunately, molecular subtypes of 40% of patients at first diagnosis and 20% of patients at recurrent disease were missed in the study since Her2 was not routinely performed at the beginning of the interval time.
IBTR affects about 7% of treated women with curative intent, and the cumulative risk of a second breast tumor increased over the years [1]. Moreover, the most common second tumor after primary BC in patient survivors is a second breast tumor [16]. The standard treatment for IBTR is a salvage mastectomy in the majority of cases [17]. Breast reconstruction is generally offered at the same time of salvage mastectomy, although irradiated tissues may required more sophisticated techniques for reconstruction. In fact, previous total breast irradiation (that is an integral part of breast conservation) represents one of the most known risk factors for developing capsular contracture after breast implant surgery [18e21]. Therefore, implant based reconstructions in irradiated breast are frequently contraindicated; fibrosis of the pectoral major muscle is a great limitation for breast reconstruction in the submuscular place. In case of irradiated breasts, classical autologous flaps or, more recently, acellular dermal matrices are indicated. Among the flaps, LD is often used as autologous transfer
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
4
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx Table 1 Patients’ characteristics (N ¼ 111). Total (N ¼ 111) Baseline characteristics Age (year), median (min-max) BMI (kg/m2), median (min-max) Smokers, N (%) Presence of diabetes, N (%) Menopausal status, N (%)
Breast, N (%) Characteristics at primary Histology, N (%)
pT, N (%)
Grade, N (%)
Subtype, N (%)
Characteristics at recurrence Reconstruction surgery, N (%) Presence of prosthesis, N (%) Prosthesis volume, median (min-max) Contralateral surgery, N (%)
Histology, N (%)
pT, N (%)
Lymph-nodes status, N (%)
Grade, N (%)
Missing No Yes No Yes Pre-menopause Post-menopause Peri-menopause Left Right
46 (27e71) 22 (15e42) 2 79 (71.2) 32 (28.8) 109 (98.2) 2 (1.8) 57 (51.4) 51 (45.9) 3 (2.7) 55 (49.5) 56 (50.5)
Invasive ductal carcinoma Invasive lobular carcinoma Mucinous carcinoma Ductal carcinoma in situ Invasive tubular carcinoma Invasive tubule-lobular carcinoma Metaplastic carcinoma pT1 pT2 pT4 IS X Missing Not performed 1 2 3 Missing Luminal A Luminal B (Ki67 20%) Luminal B (HER2 positive) HER2 positive Triple negative Missing
75 (67.6) 5 (4.5) 1 (0.9) 17 (15.3) 1 (0.9) 1 (0.9) 11 (9.9) 56 (50.5) 20 (18.0) 1 (0.9) 17 (15.3) 1 (0.9) 16 (14.4) 2 (1.8) 9 (8.1) 32 (28.8) 39 (35.1) 29 (26.1) 15 (13.5) 26 (23.4) 9 (8.1) 4 (3.6) 12 (10.8) 45 (40.5)
LD flap alone LD flap plus prosthesis No Yes
19 (17.1) 92 (82.9) 19 (17.1) 92 (82.9) 270 (80e525) 9 (8.1) 13 (11.7) 26 (23.4) 16 (14.4) 47 (42.3) 67 (60.4) 7 (6.3) 2 (1.8) 9 (8.1) 13 (11.7) 2 (1.8) 1 (0.9) 2 (1.8) 1 (0.9) 1 (0.9) 6 (5.4) 11 (9.9) 56 (50.5) 23 (20.7) 4 (3.6) 13 (11.7) 2 (1.8) 2 (1.8) 48 (43.2) 8 (7.2) 3 (2.7) 52 (46.8) 6 (5.4) 24 (21.6) 33 (29.7)
Mammaplasty reduction Mammaplasty augmentation Mastopexy Other None Invasive ductal carcinoma Invasive lobular carcinoma Mucinous carcinoma Negative Ductal carcinoma in situ Mixed ductal and lobular carcinoma Metaplastic cancer Other cancer e non breast Paget disease Mixed ductal and mucinous carcinoma Missing 0 pT1 pT2 pT3 IS X Missing pN0 pN1 pN2 X 1 2 3
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
5
Table 1 (continued ) Total (N ¼ 111) Missing No Yes Missing Luminal A Luminal B (Ki67 20%) Luminal B (HER2 positive) HER2 positive Triple negative Missing
Vascular Invasion, N (%)
Subtype, N (%)
48 65 23 23 12 33 16 18 10 22
(43.2) (58.6) (20.7) (20.7) (10.8) (29.7) (14.4) (16.2) (9.0) (19.8)
Table 2 Post-operative complications after reconstruction surgery due to recurrence (N ¼ 111). Total (N ¼ 111) Post-operative complication, N (%) Complication at the reconstructed breast, N (%)
Complication at the contralateral breast, N (%) Complication at the back, N (%)
a b
a
No Yes None Diastasis Hematoma Necrosis Seroma Infection None Necrosis No Diastasis Hematoma
92 (82.9) 19 (17.1b) 96 (86.5) 2 (1.8) 1 (0.9) 7 (6.3) 4 (3.6) 1 (0.9) 110 (99.1) 1 (0.9) 106 (95.5) 1 (0.9) 4 (3.6)
N ¼ 68 PTs had seroma. 95% confidence interval: 10.6%e25.4%.
Fig. 1. Overall survival since surgery on breast recurrence (N ¼ 111).
(exclusively autologous tissue and no implant associated) or in combination with implant placement. Unfortunately, few data exist about breast reconstruction for surgery of IBTRs. However, immediate reconstruction after salvage mastectomy is routinely offered to patients. Spear et al. [22] and Disa et al. [23] demonstrated the feasibility of LD flap reconstruction in addition of definitive prosthesis implant or temporary tissue expander. Interestingly, Disa et al. [23]
analyzed retrospectively 57 patients who underwent immediate LD/prosthetic reconstruction following salvage mastectomy for IBTR. A total of 29.8% post-operative complications were identified, being 7% major and 22.8% minor complications. Overall latissimus dorsi flap survival was 100%. Two-stage, latissimus dorsi/tissue expandereimplant reconstruction was performed in 89% of the total cohort (51 of 57). The Authors stated that LD flap facilitate implant reconstruction with a low rate of complications and a good overall aesthetic result. No information has been reported about oncologic outcomes. More recently, van Huizum et al. [24] specifically compared immediate reconstruction with LD after salvage mastectomy in irradiated breasts to the widely accepted secondary breast reconstructions. In the first subgroup of patients, they include a heterogeneous population of local relapsing women, BRCA mutated patients undergoing risk reducing mastectomy and women requiring mastectomy for severe fibrosis of the irradiated breast. They observed a 27% rate of major complications requiring further surgery in both groups and implant loss at the side of salvage mastectomy was 11,8%. The disease-free survival in the group of mastectomy and immediate reconstruction was 94% after an average follow-up period of 41.5 months. Similarly to the Dutch series, we retrospectively collected patient demographic data and data on previous radiotherapy, salvage surgery, reconstructive surgery, post-operative complications and oncologic outcomes from a prospectively maintained institutional database. To our knowledge, our study represents the largest series of local recurrent BC patients undergoing salvage mastectomy and immediate reconstruction with LD at a single-institute with a prolonged follow-up. Moreover, a complete analysis of clinicpathologic features, OS, DFS is added. Overall, we observed lower postoperative complications (17.1%), being the majority of them minor complications (Table 2) not requiring any further surgery. In
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
6
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
Fig. 2. Overall survival since surgery on breast recurrence by histological subtypes (N ¼ 89).
Fig. 3. Disease free survival since surgery on breast recurrence (N ¼ 111).
Fig. 4. Cumulative incidence of locoregional recurrences since surgery on breast recurrence (N ¼ 111).
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
7
Fig. 5. Disease free survival since surgery on breast recurrence by histological subtypes (N ¼ 89).
fact, seroma formation and minor wound dehiscence were conservatively treated at outpatient clinic. Implant loss at the side of mastectomy occurred in 4,3% of patients (4 out of 92 implants). In one case it wasn't due to local complications but the implant was removed for further surgery for local relapse. Certainly, our cohort of consecutive relapsing patients undergoing LD reconstruction is selected and includes a minority of smokers, obese and diabetic women. It explains why complication rates were not extraordinarily high. During the preoperative counseling candidates for reconstruction are selected according to patient desires, the presence of comorbidities and surgical risk factors and the oncologic status. We didn't specifically investigate back and shoulder function and quality of life after LD reconstruction in this subpopulation of patients since we focused on the oncologic safety of the procedure. However, we addressed this issue in our previous paper that specifically investigated shoulder function after LD reconstruction [25]. It is a prospective cohort study of patients undergoing LD reconstruction in the same interval time, both immediate and delayed and including 67,3% of relapsing patients after breast conservation. The majority of patients showed a joint recovery superior to 80% in all joint movements examined. Disabilities of the Arm, Shoulder and Hand questionnaire revealed minimal disability and it appeared to decrease in all sports and in particular in those involving LD practice. Similarly, cosmetic outcomes, capsular contracture rate and the
need of further surgery after LD reconstruction are not specifically investigated in this study. We previously published a small series of locally relapsing patients undergoing LD reconstruction between 2001 and 2007 [12]. We specifically focused on postoperative complications and cosmetic outcomes, demonstrating that LD reconstruction is feasible in relapsing patients. With regard to oncologic outcomes, 5-year overall survival was 92% in our series. Therefore, our data confirmed that LD reconstruction with or without implant in the subpopulation of local relapsing women is a safe procedure. Unfortunately, due the low number of patients included in each molecular subgroup, we can not drive any conclusion about disease free interval and subsequent relapse and/or death according to BC subtypes. In conclusion, immediate LD reconstruction can be safely offered to patients with isolated local or loco regional recurrence of BC. Surgical planning is tailored to each patient according to therapeutic needs. Immediate reconstruction can be securely considered an integral part of the management of IBTR. Human and animal rights All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
8
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
Informed consent Informed consent was obtained from all individual participants included in the study. The local scientific committee approved the manuscript. Declaration of competing interest The authors declare that they have no conflict of interest. References [1] Corso G, Maisonneuve P, Santomauro GI, et al. Ipsilateral breast tumor reappearance and contralateral breast cancer after primary breast cancer treatment: a comprehensive retrospective study of 15,168 patients. Oncology 2018;95(3):147e55. [2] Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Canc Res Treat 2012;133(3):813e41. [3] Wapnir IL, Gelber S, Anderson SJ, et al. Poor prognosis after second locoregional recurrences in the CALOR trial. Ann Surg Oncol 2017;24(2):398e406. [4] Meyers MO, Klauber-Demore N, Ollila DW, et al. Impact of breast cancer molecular subtypes on locoregional recurrence in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. Ann Surg Oncol 2011;18(10):2851e7. [5] DeLong MR, Tandon VJ, Rudkin GH, Da Lio AL. Latissimus dorsi flap breast reconstruction-A nationwide inpatient sample review. Ann Plast Surg 2017;78(5 Suppl 4):S185e8. [6] Hammond DC. Latissimus dorsi flap breast reconstruction. Plast Reconstr Surg 2009;124(4):1055e63. [7] Kokosis G, Khavanin N, Nahabedian M. Latissimus dorsi musculocutaneous flap for complex breast reconstruction: indications, outcomes and a proposed algorithm. Plast Reconstr Surg - Glob Open 2019;7(8):e2382. [8] Hammond DC. Postmastectomy reconstruction of the breast using the latissimus dorsi musculocutaneous flap. Cancer J 2008;14(4):248e52. [9] Kodaganur S, Paga U, Ram A, et al. Feasibility, safety, and clinical outcomes following latissimus dorsi flap reconstruction in breast cancer- an Institutional study. Breast J 2018;24(5):843e5. [10] Nedumpara T, Jonker L, Williams MR. Impact of immediate breast reconstruction on breast cancer recurrence and survival. Breast 2011;20(5): 437e43. [11] Petit JY, Gentilini O, Rotmensz N, et al. Oncological results of immediate breast reconstruction: long term follow-up of a large series at a single institution.
Breast Canc Res Treat 2008;112(3):545e9. [12] Garusi C, Lohsiriwat V, Brenelli F, et al. The value of latissimus dorsi flap with implant reconstruction for total mastectomy after conservative breast cancer surgery recurrence. Breast 2011;20(2):141e4. [13] Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol 2013;24(9):2206e23. [14] International Commission on Radiation Units and Measurements. Prescribing, recording, and reporting photon beam therapy: ICRU report 50. Bethesda: International Commission on Radiation Units and Measurements; 1993. [15] Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies–improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol 2015;26(8): 1533e46. [16] Corso G, Veronesi P, Santomauro GI, et al. Multiple primary non-breast tumors in breast cancer survivors. J Cancer Res Clin Oncol 2018;144(5):979e86. [17] Salvadori B, Marubini E, Miceli R, et al. Reoperation for locally recurrent breast cancer in patients previously treated with conservative surgery. Br J Surg 1999;86(1):84e7. [18] Lin KY, Blechman AB, Brenin DR. Implant-based, two-stage breast reconstruction in the setting of radiation injury: an outcome study. Plast Reconstr Surg 2012;129(4):817e23. [19] Bachour Y, Bargon CA, de Blok CJM, Ket JCF, Ritt MJPF, Niessen FB. Risk factors for developing capsular contracture in women after breast implant surgery: a systematic review of the literature. J Plast Reconstr Aesthet Surg 2018;71(9): e29e48. [20] Straub JM, New J, Hamilton CD, Lominska C, Shnayder Y, Thomas SM. Radiation-induced fibrosis: mechanisms and implications for therapy. J Cancer Res Clin Oncol 2015;141(11):1985e94. €rr W, Hendry JH. Consequential late effects in normal tissues. Radiother [21] Do Oncol 2001;61(3):223e31. [22] Spear SL, Boehmler JH, Taylor NS, Prada C. The role of the latissimus dorsi flap in reconstruction of the irradiated breast. Plast Reconstr Surg 2007;119(1): 1e9. discussion 10-1. [23] Disa JJ, McCarthy CM, Mehrara BJ, Pusic AL, Cordeiro PG. Immediate latissimus dorsi/prosthetic breast reconstruction following salvage mastectomy after failed lumpectomy/irradiation. Plast Reconstr Surg 2008;121(4). 159e-64e. [24] van Huizum MA Hage, Rutgers EJ, Hoornweg MJ. Immediate breast reconstruction with a myocutaneous latissimus dorsi flap and implant following skin-sparing salvage mastectomy after irradiation as part of breast-conserving therapy. J Plast Reconstr Surg 2016;69(8):1080e6. [25] Garusi C, Manconi A, Lanni G, et al. Shoulder function after breast reconstruction with the latissimus dorsi flap: a prospective cohort study combining DASH score and objective evaluation. Breast 2016;27:78e86.
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
Contents lists available at ScienceDirect
European Journal of Surgical Oncology journal homepage: www.ejso.com
Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer F. De Lorenzi a, *, 1, G. Corso b, c, 1, F. Botta d, A. Invento b, A. Marchetti a, P. Sala a, G. Vottero a, V. Bagnardi d, C. Leonardi e, P. Veronesi b, c, A. Goldhirsch f a
Division of Plastic and Reconstructive Surgery, European Institute of Oncology IRCCS, Milan, Italy Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy Department of Oncology and Hemato-Oncology, University of Milan, Italy d Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy e Division of Radiation Oncology, European Institute of Oncology, IRCCS, Milan, Italy f Multimedica, Milan, Italy b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 8 November 2019 Received in revised form 17 December 2019 Accepted 8 January 2020 Available online xxx
Background: Ipsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed. Methods: We retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction. All included patients with IBTR previously underwent conserving surgery for BC, and received a postoperative irradiation. Primary endpoints were disease free survival and overall survival. Secondary endpoints were surgical complications and reinterventions. Results: Invasive ductal cancer was the most frequent histotype (60.4%) of breast cancer reappearance. rpT1, rpT2 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Post-operative complication other than seroma occurred in 17,1% of patients, while seroma at the donor site was observed in 61.3% of cases. At 5-year after surgery overall survival was 92% (95% CI: 85%e96%) and disease free survival was 78% (95% CI: 69%e85%). Conclusions: Immediate latissimus dorsi flap reconstruction in selected patients with isolated breast tumor recurrence, which occurred after breast irradiation, provides an effective treatment with a satisfactory outcome. © 2020 Published by Elsevier Ltd.
Keywords: Breast reconstruction Breast relapse Breast cancer
Introduction About 7% of patients with primary breast cancer (BC) develop a loco-regional recurrence after primary cancer treatment, independently of surgical approach [1]. Locoregional recurrence is described as ipsilateral, in-breast tumor recurrence after lumpectomy (IBTR), chest wall recurrence after mastectomy, or recurrence in the ipsilateral axillary or supraclavicular lymph nodes (less commonly infraclavicular and/or internal mammary nodes). Since
* Corresponding author. Division of Plastic and Reconstructive Surgery, European Institute of Oncology IRCCS, via G. Ripamonti 435, Milan, 20141, Italy E-mail address: [email protected] (F. De Lorenzi). 1 Contributed equally.
the natural history of the disease is different in patients with either luminal disease, with HER2 overexpression, or with triple negative disease, such three different subpopulations can be identified. The different molecular subtypes reflect the biological diversity of breast cancer and they have proven to be a powerful predictor of survival and distant recurrence [2e4]. Because most first IBTRs are operable, management of the recurrence is aimed at control of local disease via surgical excision and selective use of radiation therapy, depending on prior treatments. Salvage mastectomy is the most common operation and latissimus dorsi (LD) flap is frequently used for breast reconstruction. Immediate reconstruction with LD flap for primary BCs has been largely described [5e9]. It has been demonstrated that it does not interfere with systemic adjuvant treatments and overall survival,
https://doi.org/10.1016/j.ejso.2020.01.015 0748-7983/© 2020 Published by Elsevier Ltd.
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
2
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
time to distant or local relapses [10]. It is considered a safe option for both invasive and in situ cancers, [11]. Only few data exist regarding the use of LD flap in patients with isolated local or loco regional recurrence of BC [12]. The aim of the study is to investigate the BC related events, or death and surgery-related complications after LD reconstructions in patients who had a local relapse (without identified systemic disease). Patients and methods Between 2002 and 2011, in the European Institute of Oncology (IEO) institutional data base we identified 111 consecutive patients who had an isolated local recurrence and who underwent immediate LD reconstruction. All patients who developed IBTR previously underwent conserving surgery for BC, followed by postoperative irradiation. Clinical and pathological data as age at cancer onset, body mass index (BMI), TNM classification, histotype and smoking status were recorded. Detected levels of ER, PgR, and HER2 overexpression and/or amplification (FISH test) and Ki-67 were used to define subsets of breast cancer molecular subtypes: Luminal Aelike tumors are ERpositive and HER2-negative with low Ki-67 expression (<14%) or with intermediate Ki-67 expression (14%e19%) and high PgR levels (20%); Luminal Belike tumors are ER-positive with intermediate Ki-67 expression (14%e19%) and low PgR levels (<20%) or with high Ki-67 expression (20%) or ER-positive and HER2-positive; Triple negative tumors are ER-, PgR- and HER2-negative and HER2 positive tumors are ER- and PgR-negative and HER2-positive [13]. Patients presenting bone and/or soft tissue (beyond regional lymph nodes) and/or visceral relapses as first event were excluded from the study group as well as patients who received exclusive electron intra-operative radiotherapy and/or intraoperative boost and external irradiation as primary irradiation. Objectives Primary endpoints were to assess disease free interval (DFI) and subsequent relapse (type and organ) and/or death in the entire cohort and according to BC subtypes [13] (i.e. luminal A, luminal B (Ki67 20%), luminal B (HER2 positive), HER2 positive-not luminal, and triple negative). Secondary endpoints were surgery-related complications and their potential influence on oncologic outcomes (minor complications not requiring further surgery; major complications requiring re-intervention). Previous radiotherapy Three-dimensional conformal radiotherapy was delivered to the whole breast with two opposed tangential fields of 6-MV photons or mixed energy 6e18 MV in case of large breast. A boost dose was always applied. The treatment schedule consisted of either conventional fractionation (50 Gy in 25 fractions followed by sequential boost of 10 Gy in 5 fractions with electrons) or moderate hypo fractionation (45 Gy in 20 fractions and concomitant boost of 5 Gy, delivered with photons or electrons). All patients underwent CT simulation and were treated in supine position with both the arms raised above the head. The clinical target volume (CTV) was delineated on the CT scan. The planning target volume was created by applying 1.5-cm margins to the CTV in craniocaudal directions and towards the air. The lateral border was at the midaxillary line. Regarding the posterior margin, care was taken not to exceed 2.5 cm for the central lung distance and 1 cm for the maximal heart
distance in left-sided breast. Multileaf collimator and optimized beam set-up were used to meet the dose -volume constraints for contralateral breast (no point receiving >15% of the prescribed dose, PD), heart (10% of the heart not exceeding 25 Gy, V25 10%), and ipsilateral lung (20% of the lung not exceeding 20 Gy, V20 20%). The treatment plans were normalized at the International Commission on Radiation Units and Measurements (ICRU) reference point. Wedge compensation was used to achieve a uniform dose distribution across the PTV (5% to þ7% of the PD) as recommended by ICRU report 50 [14]. Preoperative planning and design The function of the latissimus dorsi flap was clinically assessed; good function generally indicates that the thoracodorsal pedicle is intact. In case of any doubt (i.e. previous surgery and scars in the dorsal and axillary areas), ultrasound examination with Doppler of the axillary region was performed. The reconstruction was designed with the patient in a standing position. The dorsal skin paddle was marked according to natural folds of skin and fat in the dorsal region and according to incisions and skin removal at the mastectomy site. Therefore, flap design has been tailored to each patient. In all the patients, the amount of dorsal skin available was carefully assessed using the pinch test so that closure was performed entirely free from tension. Operative technique and positioning and modeling of the flap After mastectomy and axillary surgery were carried out, the patient was placed in a lateral position with the arm in abduction to open the axillary hollow. The identification of the thoracodorsal pedicle was assessed through the mastectomy or axillary skin incision. Afterwards, the dissection differed in case of autologous or latissimus dorsi flap and implant. In case of autologous pedicled transfer, the dorsal skin paddle was incised until the fascia superficialis and dissection followed the deep aspect of the fascia superficialis, taking in care to leave the deep fat on the muscle. Fatty areas in the scapular region, from the anterior margin of the latissimus dorsi and from the love handles were included within the flap as well as deep fat. In case of pedicled transfer and implant reconstruction, the dorsal skin paddle was incised directly to the fascia profunda, just above the muscle and dissection followed muscular fibers in any direction. The anterior margin of the latissimus dorsi was first identified, and when it was completely undermined the distal part was transacted. The dissection continued in the submuscular deep space, carefully ligating or coagulating the accessory pedicles. The pedicle, already identified anteriorly from the mastectomy/axillary incision, was approached posteriorly by releasing the teres major from the latissimus. The pedicle of the serratus anterior was generally followed up to the Y-bifurcation thoracodorsal vessels. In all patients the thoracodorsal nerve to the latissimus dorsi muscle was not divided. To make flap transposition easier and without tension, in some cases was necessary the partial proximal section of the tendon. The flap was transposed to the breast area via a subcutaneous tunnel. The donor site was closed after irrigation of the whole area in order to obtain perfect hemostasis. Quilting sutures were not always used. One or two suction drains were placed in the back. Positioning and modeling of the flap differed according to mastectomy scar and the necessity of replace part of the breast skin. If possible, original breast skin was preserved and the skin paddle almost totally de epithelialized, avowing patch effect of the dorsal skin.
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
A suction drain was inserted. Modeling differed in case of autologous reconstructions or with the use of implants. In both cases, the patient was put in a sitting position on the surgical table to check the shape and volume of the reconstructed breast. In case of implant and latissimus, sizers were used to choose the right implant. Follow up Following surgery, all patients were discussed during the weekly multidisciplinary meeting attended by plastic and breast dedicated surgeons, medical oncologists, radiation oncologists and pathologists. The decision for adjuvant systemic treatment was made on the basis of biological features, staging, previously received treatments and comorbidities, according to international approved guidelines regularly updated (St.Gallen) [15]. The clinical follow-up of the different subpopulations was similar and planned every six months. A radiological examination of the breasts was performed every year (including bilateral ultrasound and mammogram of the healthy breast) or more frequently in case of clinical suspicion. Implant integrity was checked annually with ultrasound, only in case of suspected rupture MRI was recommended. Liver and bone were checked every year as well as biological markers.
3
Breast reconstruction was performed with autologous LD in 17.1% of patients and in association with implant in 82.9% of cases. Post-operative complications Seroma formation in the donor area occurred in 68 out of 111 flaps (61.3%). They were all treated conservatively by aspiration at outpatient clinic. Excluding these seromas, which have not been considered a complication but an expected draw back of the technique, in total we observed postoperative complications in 17.1% of patients. The most frequent complications at the reconstructed breast were mastectomy skin flap necrosis (6.7%) and seroma formation (3,6%). Even seromas at the reconstructed breast were conservatively treated. The most frequent complication at the donor area of the flap was hematoma formation that occurred in 3,6% of patients. No significant difference was observed among the different molecular subtypes of cancer reappearance with regard to overall post-operative complications. Similarly, no specific complication was associated with any subgroup of patients (Table 2). Implant loss at the side of salvage mastectomy occurred in four patients (4,3%). In two patients it was due early necrosis of mastectomy flaps, in one case to wound dehiscence at the side of reconstruction and in one other patient the implant was removed due to further surgery for local relapse in the interval study.
Statistical analysis Oncologic outcomes A descriptive analysis was performed for patients' and tumors’ characteristics evaluated both at the time of primary and recurrence surgeries, and post-operative complications after reconstruction surgery due to recurrence. Continuous data were reported as median and interquartile range (IQR) and categorical data as counts ad percentages (%). Moreover, overall survival (OS) and disease-free survival (DFS) functions were estimated applying the Kaplan-Meier method and, in order to evaluate differences among BC subtypes, the log-rank test was performed. The cumulative incidence of locoregional recurrences was calculated using Kalbfleisch and Prentice method, with distant metastases, contralateral recurrences, other primaries and deaths as first observed event considered as competing events. A P-value<0.05 was considered statistically significant. All analyses were performed with the use of SAS software, version 9.4 (SAS Institute, Cary; NC).
Overall survival (OS) was respectively 92% (95% CI: 85%e96%) at 5-year and 82% (95% CI: 70%e89%) at 10-year after surgery in the all population (Fig. 1). Patients with biologically aggressive disease at diagnosis (Luminal B or HER 2 positive) had worse OS at 5 years than others (94% (95% CI: 63%e99%) (Fig. 2). The overall DFS was 78% (95% CI: 69%e85%) at 5 year (Fig. 3) and 63% (95% CI: 50%e73%) at 10 year. The 5- and 10-yr cumulative incidence of locoregional recurrences was, respectively, 7% (95% CI: 3%e13%) and 10% (95% CI: 5%e18%) (Fig. 4). Considering the different sub-groups, DFS at 5-year was 82% (95% CI: 45%e95%) in Luminal A group, compared with 71% (95% CI: 51%e83%) and 93% (95% CI: 59%e99%) in Luminal B group (Ki67 20%) and in Luminal B group (HER 2 positive), respectively (Fig. 5). Due to the low number of the stratified groups, DFS at 10-year was omitted.
Results Discussion Patients’ characteristics Patients’ characteristics are described in Table 1. The most frequent histotypes at primary were invasive ductal carcinoma (IDC) in 67.6% of patients and ductal carcinoma in situ in 15.3%. All patients presented positive axillary nodes at first onset. Luminal B (Ki67 20%) was the most frequent subtype identified (23.4%). Invasive ductal cancer was the most frequent histotype (60.4%) of BC reappearance. rpT1, rpT2 N0 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the all patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Luminal B (hormone receptor positive and Ki67 20%) was the most frequent subtype even among IBTRs (29.7%). Unfortunately, molecular subtypes of 40% of patients at first diagnosis and 20% of patients at recurrent disease were missed in the study since Her2 was not routinely performed at the beginning of the interval time.
IBTR affects about 7% of treated women with curative intent, and the cumulative risk of a second breast tumor increased over the years [1]. Moreover, the most common second tumor after primary BC in patient survivors is a second breast tumor [16]. The standard treatment for IBTR is a salvage mastectomy in the majority of cases [17]. Breast reconstruction is generally offered at the same time of salvage mastectomy, although irradiated tissues may required more sophisticated techniques for reconstruction. In fact, previous total breast irradiation (that is an integral part of breast conservation) represents one of the most known risk factors for developing capsular contracture after breast implant surgery [18e21]. Therefore, implant based reconstructions in irradiated breast are frequently contraindicated; fibrosis of the pectoral major muscle is a great limitation for breast reconstruction in the submuscular place. In case of irradiated breasts, classical autologous flaps or, more recently, acellular dermal matrices are indicated. Among the flaps, LD is often used as autologous transfer
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
4
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx Table 1 Patients’ characteristics (N ¼ 111). Total (N ¼ 111) Baseline characteristics Age (year), median (min-max) BMI (kg/m2), median (min-max) Smokers, N (%) Presence of diabetes, N (%) Menopausal status, N (%)
Breast, N (%) Characteristics at primary Histology, N (%)
pT, N (%)
Grade, N (%)
Subtype, N (%)
Characteristics at recurrence Reconstruction surgery, N (%) Presence of prosthesis, N (%) Prosthesis volume, median (min-max) Contralateral surgery, N (%)
Histology, N (%)
pT, N (%)
Lymph-nodes status, N (%)
Grade, N (%)
Missing No Yes No Yes Pre-menopause Post-menopause Peri-menopause Left Right
46 (27e71) 22 (15e42) 2 79 (71.2) 32 (28.8) 109 (98.2) 2 (1.8) 57 (51.4) 51 (45.9) 3 (2.7) 55 (49.5) 56 (50.5)
Invasive ductal carcinoma Invasive lobular carcinoma Mucinous carcinoma Ductal carcinoma in situ Invasive tubular carcinoma Invasive tubule-lobular carcinoma Metaplastic carcinoma pT1 pT2 pT4 IS X Missing Not performed 1 2 3 Missing Luminal A Luminal B (Ki67 20%) Luminal B (HER2 positive) HER2 positive Triple negative Missing
75 (67.6) 5 (4.5) 1 (0.9) 17 (15.3) 1 (0.9) 1 (0.9) 11 (9.9) 56 (50.5) 20 (18.0) 1 (0.9) 17 (15.3) 1 (0.9) 16 (14.4) 2 (1.8) 9 (8.1) 32 (28.8) 39 (35.1) 29 (26.1) 15 (13.5) 26 (23.4) 9 (8.1) 4 (3.6) 12 (10.8) 45 (40.5)
LD flap alone LD flap plus prosthesis No Yes
19 (17.1) 92 (82.9) 19 (17.1) 92 (82.9) 270 (80e525) 9 (8.1) 13 (11.7) 26 (23.4) 16 (14.4) 47 (42.3) 67 (60.4) 7 (6.3) 2 (1.8) 9 (8.1) 13 (11.7) 2 (1.8) 1 (0.9) 2 (1.8) 1 (0.9) 1 (0.9) 6 (5.4) 11 (9.9) 56 (50.5) 23 (20.7) 4 (3.6) 13 (11.7) 2 (1.8) 2 (1.8) 48 (43.2) 8 (7.2) 3 (2.7) 52 (46.8) 6 (5.4) 24 (21.6) 33 (29.7)
Mammaplasty reduction Mammaplasty augmentation Mastopexy Other None Invasive ductal carcinoma Invasive lobular carcinoma Mucinous carcinoma Negative Ductal carcinoma in situ Mixed ductal and lobular carcinoma Metaplastic cancer Other cancer e non breast Paget disease Mixed ductal and mucinous carcinoma Missing 0 pT1 pT2 pT3 IS X Missing pN0 pN1 pN2 X 1 2 3
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
5
Table 1 (continued ) Total (N ¼ 111) Missing No Yes Missing Luminal A Luminal B (Ki67 20%) Luminal B (HER2 positive) HER2 positive Triple negative Missing
Vascular Invasion, N (%)
Subtype, N (%)
48 65 23 23 12 33 16 18 10 22
(43.2) (58.6) (20.7) (20.7) (10.8) (29.7) (14.4) (16.2) (9.0) (19.8)
Table 2 Post-operative complications after reconstruction surgery due to recurrence (N ¼ 111). Total (N ¼ 111) Post-operative complication, N (%) Complication at the reconstructed breast, N (%)
Complication at the contralateral breast, N (%) Complication at the back, N (%)
a b
a
No Yes None Diastasis Hematoma Necrosis Seroma Infection None Necrosis No Diastasis Hematoma
92 (82.9) 19 (17.1b) 96 (86.5) 2 (1.8) 1 (0.9) 7 (6.3) 4 (3.6) 1 (0.9) 110 (99.1) 1 (0.9) 106 (95.5) 1 (0.9) 4 (3.6)
N ¼ 68 PTs had seroma. 95% confidence interval: 10.6%e25.4%.
Fig. 1. Overall survival since surgery on breast recurrence (N ¼ 111).
(exclusively autologous tissue and no implant associated) or in combination with implant placement. Unfortunately, few data exist about breast reconstruction for surgery of IBTRs. However, immediate reconstruction after salvage mastectomy is routinely offered to patients. Spear et al. [22] and Disa et al. [23] demonstrated the feasibility of LD flap reconstruction in addition of definitive prosthesis implant or temporary tissue expander. Interestingly, Disa et al. [23]
analyzed retrospectively 57 patients who underwent immediate LD/prosthetic reconstruction following salvage mastectomy for IBTR. A total of 29.8% post-operative complications were identified, being 7% major and 22.8% minor complications. Overall latissimus dorsi flap survival was 100%. Two-stage, latissimus dorsi/tissue expandereimplant reconstruction was performed in 89% of the total cohort (51 of 57). The Authors stated that LD flap facilitate implant reconstruction with a low rate of complications and a good overall aesthetic result. No information has been reported about oncologic outcomes. More recently, van Huizum et al. [24] specifically compared immediate reconstruction with LD after salvage mastectomy in irradiated breasts to the widely accepted secondary breast reconstructions. In the first subgroup of patients, they include a heterogeneous population of local relapsing women, BRCA mutated patients undergoing risk reducing mastectomy and women requiring mastectomy for severe fibrosis of the irradiated breast. They observed a 27% rate of major complications requiring further surgery in both groups and implant loss at the side of salvage mastectomy was 11,8%. The disease-free survival in the group of mastectomy and immediate reconstruction was 94% after an average follow-up period of 41.5 months. Similarly to the Dutch series, we retrospectively collected patient demographic data and data on previous radiotherapy, salvage surgery, reconstructive surgery, post-operative complications and oncologic outcomes from a prospectively maintained institutional database. To our knowledge, our study represents the largest series of local recurrent BC patients undergoing salvage mastectomy and immediate reconstruction with LD at a single-institute with a prolonged follow-up. Moreover, a complete analysis of clinicpathologic features, OS, DFS is added. Overall, we observed lower postoperative complications (17.1%), being the majority of them minor complications (Table 2) not requiring any further surgery. In
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
6
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
Fig. 2. Overall survival since surgery on breast recurrence by histological subtypes (N ¼ 89).
Fig. 3. Disease free survival since surgery on breast recurrence (N ¼ 111).
Fig. 4. Cumulative incidence of locoregional recurrences since surgery on breast recurrence (N ¼ 111).
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
7
Fig. 5. Disease free survival since surgery on breast recurrence by histological subtypes (N ¼ 89).
fact, seroma formation and minor wound dehiscence were conservatively treated at outpatient clinic. Implant loss at the side of mastectomy occurred in 4,3% of patients (4 out of 92 implants). In one case it wasn't due to local complications but the implant was removed for further surgery for local relapse. Certainly, our cohort of consecutive relapsing patients undergoing LD reconstruction is selected and includes a minority of smokers, obese and diabetic women. It explains why complication rates were not extraordinarily high. During the preoperative counseling candidates for reconstruction are selected according to patient desires, the presence of comorbidities and surgical risk factors and the oncologic status. We didn't specifically investigate back and shoulder function and quality of life after LD reconstruction in this subpopulation of patients since we focused on the oncologic safety of the procedure. However, we addressed this issue in our previous paper that specifically investigated shoulder function after LD reconstruction [25]. It is a prospective cohort study of patients undergoing LD reconstruction in the same interval time, both immediate and delayed and including 67,3% of relapsing patients after breast conservation. The majority of patients showed a joint recovery superior to 80% in all joint movements examined. Disabilities of the Arm, Shoulder and Hand questionnaire revealed minimal disability and it appeared to decrease in all sports and in particular in those involving LD practice. Similarly, cosmetic outcomes, capsular contracture rate and the
need of further surgery after LD reconstruction are not specifically investigated in this study. We previously published a small series of locally relapsing patients undergoing LD reconstruction between 2001 and 2007 [12]. We specifically focused on postoperative complications and cosmetic outcomes, demonstrating that LD reconstruction is feasible in relapsing patients. With regard to oncologic outcomes, 5-year overall survival was 92% in our series. Therefore, our data confirmed that LD reconstruction with or without implant in the subpopulation of local relapsing women is a safe procedure. Unfortunately, due the low number of patients included in each molecular subgroup, we can not drive any conclusion about disease free interval and subsequent relapse and/or death according to BC subtypes. In conclusion, immediate LD reconstruction can be safely offered to patients with isolated local or loco regional recurrence of BC. Surgical planning is tailored to each patient according to therapeutic needs. Immediate reconstruction can be securely considered an integral part of the management of IBTR. Human and animal rights All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015
8
F. De Lorenzi et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
Informed consent Informed consent was obtained from all individual participants included in the study. The local scientific committee approved the manuscript. Declaration of competing interest The authors declare that they have no conflict of interest. References [1] Corso G, Maisonneuve P, Santomauro GI, et al. Ipsilateral breast tumor reappearance and contralateral breast cancer after primary breast cancer treatment: a comprehensive retrospective study of 15,168 patients. Oncology 2018;95(3):147e55. [2] Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Canc Res Treat 2012;133(3):813e41. [3] Wapnir IL, Gelber S, Anderson SJ, et al. Poor prognosis after second locoregional recurrences in the CALOR trial. Ann Surg Oncol 2017;24(2):398e406. [4] Meyers MO, Klauber-Demore N, Ollila DW, et al. Impact of breast cancer molecular subtypes on locoregional recurrence in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. Ann Surg Oncol 2011;18(10):2851e7. [5] DeLong MR, Tandon VJ, Rudkin GH, Da Lio AL. Latissimus dorsi flap breast reconstruction-A nationwide inpatient sample review. Ann Plast Surg 2017;78(5 Suppl 4):S185e8. [6] Hammond DC. Latissimus dorsi flap breast reconstruction. Plast Reconstr Surg 2009;124(4):1055e63. [7] Kokosis G, Khavanin N, Nahabedian M. Latissimus dorsi musculocutaneous flap for complex breast reconstruction: indications, outcomes and a proposed algorithm. Plast Reconstr Surg - Glob Open 2019;7(8):e2382. [8] Hammond DC. Postmastectomy reconstruction of the breast using the latissimus dorsi musculocutaneous flap. Cancer J 2008;14(4):248e52. [9] Kodaganur S, Paga U, Ram A, et al. Feasibility, safety, and clinical outcomes following latissimus dorsi flap reconstruction in breast cancer- an Institutional study. Breast J 2018;24(5):843e5. [10] Nedumpara T, Jonker L, Williams MR. Impact of immediate breast reconstruction on breast cancer recurrence and survival. Breast 2011;20(5): 437e43. [11] Petit JY, Gentilini O, Rotmensz N, et al. Oncological results of immediate breast reconstruction: long term follow-up of a large series at a single institution.
Breast Canc Res Treat 2008;112(3):545e9. [12] Garusi C, Lohsiriwat V, Brenelli F, et al. The value of latissimus dorsi flap with implant reconstruction for total mastectomy after conservative breast cancer surgery recurrence. Breast 2011;20(2):141e4. [13] Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol 2013;24(9):2206e23. [14] International Commission on Radiation Units and Measurements. Prescribing, recording, and reporting photon beam therapy: ICRU report 50. Bethesda: International Commission on Radiation Units and Measurements; 1993. [15] Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies–improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol 2015;26(8): 1533e46. [16] Corso G, Veronesi P, Santomauro GI, et al. Multiple primary non-breast tumors in breast cancer survivors. J Cancer Res Clin Oncol 2018;144(5):979e86. [17] Salvadori B, Marubini E, Miceli R, et al. Reoperation for locally recurrent breast cancer in patients previously treated with conservative surgery. Br J Surg 1999;86(1):84e7. [18] Lin KY, Blechman AB, Brenin DR. Implant-based, two-stage breast reconstruction in the setting of radiation injury: an outcome study. Plast Reconstr Surg 2012;129(4):817e23. [19] Bachour Y, Bargon CA, de Blok CJM, Ket JCF, Ritt MJPF, Niessen FB. Risk factors for developing capsular contracture in women after breast implant surgery: a systematic review of the literature. J Plast Reconstr Aesthet Surg 2018;71(9): e29e48. [20] Straub JM, New J, Hamilton CD, Lominska C, Shnayder Y, Thomas SM. Radiation-induced fibrosis: mechanisms and implications for therapy. J Cancer Res Clin Oncol 2015;141(11):1985e94. €rr W, Hendry JH. Consequential late effects in normal tissues. Radiother [21] Do Oncol 2001;61(3):223e31. [22] Spear SL, Boehmler JH, Taylor NS, Prada C. The role of the latissimus dorsi flap in reconstruction of the irradiated breast. Plast Reconstr Surg 2007;119(1): 1e9. discussion 10-1. [23] Disa JJ, McCarthy CM, Mehrara BJ, Pusic AL, Cordeiro PG. Immediate latissimus dorsi/prosthetic breast reconstruction following salvage mastectomy after failed lumpectomy/irradiation. Plast Reconstr Surg 2008;121(4). 159e-64e. [24] van Huizum MA Hage, Rutgers EJ, Hoornweg MJ. Immediate breast reconstruction with a myocutaneous latissimus dorsi flap and implant following skin-sparing salvage mastectomy after irradiation as part of breast-conserving therapy. J Plast Reconstr Surg 2016;69(8):1080e6. [25] Garusi C, Manconi A, Lanni G, et al. Shoulder function after breast reconstruction with the latissimus dorsi flap: a prospective cohort study combining DASH score and objective evaluation. Breast 2016;27:78e86.
Please cite this article as: De Lorenzi F et al., Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2020.01.015