- Email: [email protected]
Lessons Learned from an Unusual Case of Inflammatory Breast Cancer
ORIGINAL REPORTS
Lessons Learned from an Unusual Case of Inflammatory Breast Cancer Andrew M. Harrison, BS,* Benjamin Zendejas, MD,† Shahzad M. Ali, MD,† Jeffrey S. Scow, MD,† and David R. Farley, MD† *Mayo Medical School and the †Department of Surgery, College of Medicine, Mayo Clinic, Rochester, Minnesota Inflammatory breast cancer (IBC) is a rare breast malignancy that is associated with poor long-term outcomes despite aggressive surgical and chemotherapeutic interventions. We recently treated a 56-year-old woman with right-sided IBC and biopsyproven cutaneous metastases to her back and left breast. She underwent chemotherapy, bilateral modified radical mastectomy, and radiation therapy. One year after diagnosis, she is currently disease-free based on positron-emission tomography (PET) imaging and repeat skin biopsies. To provide insight into the management of IBC, we present this interesting case with a reflection on important lessons to be learned. (J Surg 69: 350-354. © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.) KEYWORDS: breast cancer, metastases, inflammatory, unusual, skin, review COMPETENCY: Patient Care, Medical Knowledge, Practice Based Learning and Improvement
INTRODUCTION A 56-year-old woman was referred to our institution for a swollen right breast and right arm with concomitant erythema and pain. Extensive evaluation led to the diagnosis of advanced inflammatory breast cancer (IBC). She was treated with neoadjuvant chemotherapy which allowed for eventual surgical intervention.
CASE PRESENTATION The patient has a medical history of ductal carcinoma in situ (DCIS) of the right breast treated with lumpectomy and radiation therapy in November of 2006 at the age of 52. Chemoprevention was initiated with anastrozole, but it was discontinued after 1 year because of complaints of fatigue. Close follow-up with yearly mammograms and magnetic resonance imaging (MRI), staggered at 6-month intervals, was performed. Correspondence: Inquiries to David R. Farley, MD, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905; fax: 507-284-5196; e-mail: [email protected]
350
Nearly 3.5 years after lumpectomy she sought treatment for asymmetrical enlargement of her right arm. An ultrasound of the arm and computed tomography (CT) scan of the chest were normal. A diagnosis of right arm lymphedema was made and the patient began compression therapy. A week later—with fever and a swollen, erythematous arm—she was diagnosed with cellulitis. She underwent treatment with 5 different antibiotic regimens, but the blotchy redness involving the right upper extremity never completely resolved. In the interim, a mammogram was obtained and showed no diagnostic abnormality. Further evaluation with MRI showed evidence of new onset interstitial edema of the skin overlying the right breast with nipple thickening and enhancement. The MRI also showed axillary edema without lymphadenopathy, for which massage therapy was advised; however, no improvement in signs or symptoms was observed. The patient continued to note increasing fullness of the right upper extremity, breast, and chest wall. The areola—which she noted to have a “shiny and waxy appearance”— became more deformed, and waxy changes of the left breast similarly developed. Four months after her initial complaint of arm and breast fullness, she presented to our institution with similar complaints in addition to erythema involving the right arm, chest wall, and breast. Physical examination revealed prominent right supraclavicular lymphadenopathy and axillary firmness. The right breast was contracted and discolored by a pink hue with taut and shiny skin; it was smaller than the left breast (Fig. 1). The right nipple areolar complex was crusty and deformed with a palpable fullness. The left breast also showed patchy discoloration and central fullness to palpation. The right arm had significant lymphedema with characteristic changes of “peau d’orange”. A punch biopsy of the right breast and skin revealed grade III infiltrating ductal carcinoma that was estrogen and progesterone receptor positive and HER2/neu negative. Biopsy of skin sites on the left breast and back revealed breast cancer metastases (Fig. 2). A repeat mammogram demonstrated calcifications in the right breast suspicious for malignancy, diffuse skin thickening of the right breast, and early skin thickening of the left breast (Fig. 3). A positron emission tomography (PET)
Journal of Surgical Education • © 2012 Association of Program Directors in Surgery Published by Elsevier Inc. All rights reserved.
1931-7204/$30.00 doi:10.1016/j.jsurg.2011.10.016
FIGURE 1. Erythema is present on the right breast, right arm, and back. An abnormal right nipple areolar complex is present. The black mark present above the right nipple is from a biopsy suture.
scan found significant uptake in the right breast, bilateral axillary lymph nodes, and right neck. The patient received 4 cycles of doxorubicin and cyclophosphamide, followed by 12 weekly doses of paclitaxel, which resulted in resolution of the increased fluorodeoxyglucose (FDG) avidity on PET scanning (Fig. 4). Punch biopsies of the skin of the back and left breast were normal. She then underwent bilateral modified radical mastectomies, which revealed 3 separate foci of infiltrating ductal carcinoma of the right breast with no involvement of the right axillary lymph nodes. Involvement of metastatic adenocarcinoma in 6 of 12 left axillary lymph nodes was present along with angiolymphatic invasion (Fig. 5). The patient received radiation therapy totaling 45 Gy (25 fractions) to the anterior left and right chest as well as the posterior chest wall skin. She remains disease-free, based on PET imaging, 1 year after diagnosis.
DISCUSSION Though several reports in the literature exist on unusual presentations of breast cancer, there are several salient lessons to be learned from this case. Lesson 1. Aggressive forms of breast cancer can occur after treatment of noninvasive disease.
FIGURE 2. Skin punch biopsy sites. Metastatic infiltrating ductal carcinoma of breast is found in the right upper back (A), left lower back (C), and left breast. The left posterior back (B) and left posterior shoulder (D) reveal superficial perivascular and periadnexal lymphohistiocytic inflammation.
IBC is uncommon, representing approximately 2.5% of all cases of breast cancer.1,2 IBC occurs in the setting of an aggressive, invasive breast cancer; the diagnosis is mostly clinical, with the hallmark of overlying skin inflammation secondary to lymph channels that are clogged by tumor cells. Our patient sought treatment for the symptoms of her IBC approximately 3.5 years after a lumpectomy for DCIS of the right breast. The presence of multiple foci of infiltrating ductal carcinoma of the right breast at the time of bilateral modified radical mastectomy allows for 1 of 2 possibilities concerning the recurrence of disease. The first possibility is her IBC is the result of evolution of residual DCIS from several years prior. The second possibility is the present IBC is the result of spontaneous occurrence of new disease, to which she was likely at higher risk secondary to her previous DCIS history. Although there is no way to know for certain which is the case for our patient, the duration of the apparent disease-free interval, as evidenced by repeated mammogram and MRI, suggests the latter. Lesson 2. IBC can be difficult to diagnose, as obstructed lymphatics from the tumor can mimic inflammatory diseases or lymphedema. The difficultly in the diagnosis of IBC can result in a delay in diagnosis, as seen in this case. There are several reasons for such a delay in diagnosis to occur. First, IBC is a rare disease entity. Second, obstructed lymphatics from tumor can mimic inflammatory diseases which are more common, such as mastitis. Third, the presence of lymphedema can further obscure the presentation, as it can be easily attributed to other diseases, such as cellulitis; such was the case with our patient. As a result, she was treated first with compression therapy and eventually with multiple antibiotic regimes, which proved to be ineffective. Thus, the delay between her initial presentation and suspicion of IBC was unfortunately 4 months. Given these difficulties, such a delay is not surprising. Nonetheless, published case reports of IBC generally do not mention or discuss any significant delay between initial presentation and suspicion of IBC.3-11 Our case demonstrates that a high index of suspicion and knowledge of the patient’s previous breast cancer history is essential. Extremity lymphedema starting 4 years after a breast operation is unusual and should provoke a thorough investigation to find the cause.
Journal of Surgical Education • Volume 69/Number 3 • May/June 2012
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FIGURE 3. Right breast mammogram before chemotherapy showing calcifications in the right breast suspicious for malignancy, diffuse skin thickening of the right breast, and early skin thickening of the left breast (not shown).
Lesson 3. The treatment of patients with IBC poses unique challenges for which a multimodality approach is often needed. Our patient was treated using a multimodality approach consisting of neoadjuvant chemotherapy, surgery, and radiation therapy. Both the breast and skin metastases responded favorably to chemotherapy. This therapy consisted of doxorubicin and cyclophosphamide, followed by paclitaxel. Despite a favorable response with chemotherapy, skin biopsies to confirm absence of tumor in the skin of the back and left breast were performed. Given no cancer was seen, we were more confident that resection would lead to negative margins and the chance of sewing together skin flaps free of IBC. With resolution of FDGavid lesions on imaging studies, an aggressive plan of bilateral mastectomy and radiotherapy was pursued. These therapies were offered in hopes of adding meaningful survival benefit. In
a study from our institution, of 156 patients with nonmetastatic IBC who were treated with some form of multimodal therapy, overall and disease-free 5-year survival was 42% and 21%, respectively.12 Other studies have reported 2-, 10-, and 20-year overall survival rates of 82%, 32%-38%, and 19%, respectively using various regimens.13-16 Although radiotherapy retreatment is common across many types of cancer, median time between retreatment episodes has been observed to be longest in breast cancer (12.5 months).17 As our patient was treated several years prior with radiotherapy for DCIS, the need for repeat radiotherapy adds complexity to her care. Analysis of the clinical outcomes of repeat radiation treatments in patients with recurrent breast cancer have been the topic of investigations in multiple recent studies.18-20 Furthermore, these studies have sought to understand the late-occurring
FIGURE 4. Positron emission tomography (PET) scans demonstrating resolution of increased fluorodeoxyglucose (FDG) uptake, before (A and C) and after (B and D) chemotherapy. 352
Journal of Surgical Education • Volume 69/Number 3 • May/June 2012
FIGURE 5. Four weeks after bilateral modified radical mastectomy.
toxicity effects of repeated breast irradiation, including lymphedema, dermatitis, fibrosis, necrosis, and telangiectasia. Although there is substantial patient variation between and within studies (time between radiotherapy treatments, total radiation dose, age at diagnosis, chemotherapeutic status, etc), several important observations can be related to our patient. Specifically, the success of repeat radiotherapy in terms of local control and survival is largely dependent on the presence of gross/macroscopic tumor load.18,20 In general, these studies have found the success of local response rates to outweigh the risk posed by late-occurring toxicity effects. Although these benefits are clearer for patients with locally recurrent breast cancer, repeat radiotherapy appears to also provide acceptable outcomes for patients with distantly recurrent disease, especially when combined with local radio frequency hyperthermia therapy.18,20 Lesson 4. IBC can present with distant and unusual metastases. The presentation of IBC in our patient is unusual because of her distant skin metastases to the back. While there are extensive reviews (and many case reports) regarding the topic of cutaneous metastases from noncutaneous cancers,21-24 and indeed the most common primary source of such metastases appears to be breast adenocarcinoma, distant skin metastases are rare. To our knowledge, there is only 1 existing report of arguably distant cutaneous metastasis of IBC. Przylecki et al.25 reported skin metastases to the upper abdomen in a patient previously treated with chemotherapy, radiation therapy, hormonal therapy, and surgery, including reconstruction, for ductal carcinoma. Lesson 5. IBC is dangerous. In general, the long-term outcome with IBC is poor. Limited data on survival of IBC patients with metastases exists. Hennessy et al.26 reported in a study of metastatic IBC patients treated with primary chemotherapy and surgery, the 5-year overall survival was 82.5% when pathologic complete response of axillary lymph nodes was demonstrated, as compared with 37.1% when it was not. Sutherland et al.27 found that metastatic disease at presentation was found to decrease median survival from 3.9 to 1.7 years. Schairer et al.28 reported that the absolute risk of developing contralateral breast cancer (CBC) after IBC to be 4.9% at 2 years and 7.7% at 20 years. The
contralateral breast cancer risk for a patient with noninflammatory invasive breast cancer is about 0.8% per year.29 Based on these data, the authors argued that early recurrences are likely to be the result of metastatic disease, while later recurrences are likely the result of independent primary cancers. Multiple initial metastases to the back and contralateral breast, along with subsequent presence of metastatic adenocarcinoma in several left axillary lymph nodes postmastectomy suggests that our patient is at high risk for recurrence of disease. However, her positive response to treatment and a physical examination void of any current cutaneous lesions is encouraging.
CONCLUSIONS This report reflects on important lessons to be learned from an interesting case of a patient with IBC. Specifically, this perplexing and complex disease can occur after treatment for prior noninvasive disease. A high index of suspicion and awareness of IBC are crucial to shorten the potential delay in diagnosis that can result from the difficulty of diagnosis. Though prognosis is relatively poor for IBC, multimodality treatment with aggressive medical, surgical, and radiation therapy can achieve reasonable outcomes in selected patients. Finally, although distant skin metastases from IBC are extremely rare and may confer a poor prognosis, we remain guardedly optimistic about the longterm outcome of this upbeat patient.
REFERENCES 1. Hance KW, Anderson WF, Devesa SS, Young HA, Levine
PH. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97:966-975. 2. Robertson FM, Bondy M, Yang W, et al. Inflammatory
Journal of Surgical Education • Volume 69/Number 3 • May/June 2012
breast cancer: the disease, the biology, the treatment. CA Cancer J Clin. 2010;60:351-375. 353
3. Shigematsu H, Nakamura Y, Tanaka K, et al. A case of
inflammatory breast cancer: 20 years of follow-up. Int J Radiat Oncol Biol Phys. 2012;82:690-695.
HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment. Int J Clin Oncol. 2010;15:615-620.
17. Barton MB, Hudson HM, Delaney G, Gruver P, Liu Z.
4. Montagna E, Cancello G, Torrisi R, et al. Lapatinib and
18. Wahl AO, Rademaker A, Kiel KD, et al. Multi-institu-
metronomic capecitabine combination in an HER2-positive inflammatory breast cancer patient: a case report. Ann Oncol. 2010;21:667-668.
Patterns of retreatment by radiotherapy. Clin Oncol. 2011;23:10-18. tional review of repeat irradiation of chest wall and breast for recurrent breast cancer. Int J Radiat Oncol Biol Phys. 2008;70:477-484.
5. Chargari C, Kirova YM, Cottu P, Salmon RJ, Fourquet A.
19. Adkison JB, Kuske RR, Patel RR. Breast conserving surgery
Progressive inflammatory breast cancer in patient receiving chemotherapy: the importance of radiotherapy as a part of locoregional treatment. Radiother Oncol. 2009;90:160-161.
and accelerated partial breast irradiation after prior breast radiation therapy. Am J Clin Oncol. 2010;33:427-431.
6. Sidiropoulou Z, Ramalho L, Madureira R. Inflammatory
breast cancer: a case report. Breast Care (Basel). 2009;4: 397-399. 7. Leonard GD, Low JA, Berman AW, Swain SM. CA 125
20. Müller AC, Eckert F, Heinrich V, et al. Re-surgery and
chest wall re-irradiation for recurrent breast cancer: a second curative approach. BMC Cancer. 2011;11:197. 21. Gade JN, Kimmick G, Hitchcock MG, McMichael AJ.
Generalized cutaneous metastases from breast adenocarcinoma. J Am Acad Dermatol. 1997;37:129-130.
elevation in breast cancer: a case report and review of the literature. Breast J. 2004;10:146-149.
22. Cidon EU. Cutaneous metastases in 42 patients with can-
8. Agrawal BL, Nath AR, Glynn TP Jr, Velazco D, Garnett RF.
cer. Indian J Dermatol Venereol Leprol. 2010;76:409-412.
Unusual problems in breast cancer and a rare lung cancer case. Case 3. Simultaneous and synchronous bilateral inflammatory breast cancer. J Clin Oncol. 2003;21:2218-2220.
23. Fernandez-Flores A. Cutaneous metastases: a study of 78
9. Wood J, Collins J, Warner TF. Case of the season. Inflam-
24. Hu SC, Chen GS, Wu CS, et al. Rates of cutaneous me-
matory breast cancer. Semin Roentgenol. 2003;38:4-6. 10. Pfeiffer RB 3rd, Barber WH. Inflammatory breast cancer
presenting with acute central venous thrombosis: a case report. Am Surg. 2002;68:579-581. 11. Gordon L. Inflammatory breast cancer. Clin J Oncol Nurs.
2001;5:175-176.
biopsies from 69 patients. Am J Dermatopathol. 2010;32: 222-239. tastases from different internal malignancies: experience from a Taiwanese medical center. J Am Acad Dermatol. 2009;60:379-387. 25. Przylecki WH, Chan RK, Carty MJ, Caterson SA. Meta-
static breast cancer after delayed deep inferior epigastric perforator flap reconstruction. Ann Plast Surg. 2011;66: 233-234.
12. Smoot RL, Koch CA, Degnim AC, et al. A single-center
26. Hennessy BT, Gonzalez-Angulo AM, Hortobagyi GN, et al.
experience with inflammatory breast cancer, 1985-2003. Arch Surg. 2006;141:567-572, discussion 572-573.
Disease-free and overall survival after pathologic complete disease remission of cytologically proven inflammatory breast carcinoma axillary lymph node metastases after primary systemic chemotherapy. Cancer. 2006;106:1000-1006.
13. Dawood S, Ueno NT, Valero V, et al. Differences in survival
among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early: A large population-based study. Cancer. 2011;117:1819-1826. 14. Baldini E, Gardin G, Evagelista G, et al. Long-term results
of combined-modality therapy for inflammatory breast carcinoma. Clin Breast Cancer. 2004;5:358-363. 15. Genet D, Lejeune C, Bonnier P, et al. Concomitant in-
tensive chemoradiotherapy induction in non-metastatic inflammatory breast cancer: long-term follow-up. Br J Cancer. 2007;97:883-887. 16. Bourgier C, Pessoa EL, Dunant A, et al. Exclusive alter-
nating chemotherapy and radiotherapy in nonmetastatic
354
27. Sutherland S, Ashley S, Walsh G, Smith IE, Johnston SR.
Inflammatory breast cancer—the Royal Marsden Hospital experience: a review of 155 patients treated from 1990 to 2007. Cancer. 2010;116(11 suppl):2815-2820. 28. Schairer C, Brown LM, Mai PL. Inflammatory breast can-
cer: high risk of contralateral breast cancer compared to comparably staged non-inflammatory breast cancer. Breast Cancer Res Treat. 2011;129:117-124. 29. Rosen PP, Groshen S, Kinne DW, Hellman S. Contralat-
eral breast carcinoma: an assessment of risk and prognosis in stage I (T1N0M0) and stage II (T1N1M0) patients with 20-year follow-up. Surgery. 1989;106:904-910.
Journal of Surgical Education • Volume 69/Number 3 • May/June 2012
Lessons Learned from an Unusual Case of Inflammatory Breast Cancer Andrew M. Harrison, BS,* Benjamin Zendejas, MD,† Shahzad M. Ali, MD,† Jeffrey S. Scow, MD,† and David R. Farley, MD† *Mayo Medical School and the †Department of Surgery, College of Medicine, Mayo Clinic, Rochester, Minnesota Inflammatory breast cancer (IBC) is a rare breast malignancy that is associated with poor long-term outcomes despite aggressive surgical and chemotherapeutic interventions. We recently treated a 56-year-old woman with right-sided IBC and biopsyproven cutaneous metastases to her back and left breast. She underwent chemotherapy, bilateral modified radical mastectomy, and radiation therapy. One year after diagnosis, she is currently disease-free based on positron-emission tomography (PET) imaging and repeat skin biopsies. To provide insight into the management of IBC, we present this interesting case with a reflection on important lessons to be learned. (J Surg 69: 350-354. © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.) KEYWORDS: breast cancer, metastases, inflammatory, unusual, skin, review COMPETENCY: Patient Care, Medical Knowledge, Practice Based Learning and Improvement
INTRODUCTION A 56-year-old woman was referred to our institution for a swollen right breast and right arm with concomitant erythema and pain. Extensive evaluation led to the diagnosis of advanced inflammatory breast cancer (IBC). She was treated with neoadjuvant chemotherapy which allowed for eventual surgical intervention.
CASE PRESENTATION The patient has a medical history of ductal carcinoma in situ (DCIS) of the right breast treated with lumpectomy and radiation therapy in November of 2006 at the age of 52. Chemoprevention was initiated with anastrozole, but it was discontinued after 1 year because of complaints of fatigue. Close follow-up with yearly mammograms and magnetic resonance imaging (MRI), staggered at 6-month intervals, was performed. Correspondence: Inquiries to David R. Farley, MD, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905; fax: 507-284-5196; e-mail: [email protected]
350
Nearly 3.5 years after lumpectomy she sought treatment for asymmetrical enlargement of her right arm. An ultrasound of the arm and computed tomography (CT) scan of the chest were normal. A diagnosis of right arm lymphedema was made and the patient began compression therapy. A week later—with fever and a swollen, erythematous arm—she was diagnosed with cellulitis. She underwent treatment with 5 different antibiotic regimens, but the blotchy redness involving the right upper extremity never completely resolved. In the interim, a mammogram was obtained and showed no diagnostic abnormality. Further evaluation with MRI showed evidence of new onset interstitial edema of the skin overlying the right breast with nipple thickening and enhancement. The MRI also showed axillary edema without lymphadenopathy, for which massage therapy was advised; however, no improvement in signs or symptoms was observed. The patient continued to note increasing fullness of the right upper extremity, breast, and chest wall. The areola—which she noted to have a “shiny and waxy appearance”— became more deformed, and waxy changes of the left breast similarly developed. Four months after her initial complaint of arm and breast fullness, she presented to our institution with similar complaints in addition to erythema involving the right arm, chest wall, and breast. Physical examination revealed prominent right supraclavicular lymphadenopathy and axillary firmness. The right breast was contracted and discolored by a pink hue with taut and shiny skin; it was smaller than the left breast (Fig. 1). The right nipple areolar complex was crusty and deformed with a palpable fullness. The left breast also showed patchy discoloration and central fullness to palpation. The right arm had significant lymphedema with characteristic changes of “peau d’orange”. A punch biopsy of the right breast and skin revealed grade III infiltrating ductal carcinoma that was estrogen and progesterone receptor positive and HER2/neu negative. Biopsy of skin sites on the left breast and back revealed breast cancer metastases (Fig. 2). A repeat mammogram demonstrated calcifications in the right breast suspicious for malignancy, diffuse skin thickening of the right breast, and early skin thickening of the left breast (Fig. 3). A positron emission tomography (PET)
Journal of Surgical Education • © 2012 Association of Program Directors in Surgery Published by Elsevier Inc. All rights reserved.
1931-7204/$30.00 doi:10.1016/j.jsurg.2011.10.016
FIGURE 1. Erythema is present on the right breast, right arm, and back. An abnormal right nipple areolar complex is present. The black mark present above the right nipple is from a biopsy suture.
scan found significant uptake in the right breast, bilateral axillary lymph nodes, and right neck. The patient received 4 cycles of doxorubicin and cyclophosphamide, followed by 12 weekly doses of paclitaxel, which resulted in resolution of the increased fluorodeoxyglucose (FDG) avidity on PET scanning (Fig. 4). Punch biopsies of the skin of the back and left breast were normal. She then underwent bilateral modified radical mastectomies, which revealed 3 separate foci of infiltrating ductal carcinoma of the right breast with no involvement of the right axillary lymph nodes. Involvement of metastatic adenocarcinoma in 6 of 12 left axillary lymph nodes was present along with angiolymphatic invasion (Fig. 5). The patient received radiation therapy totaling 45 Gy (25 fractions) to the anterior left and right chest as well as the posterior chest wall skin. She remains disease-free, based on PET imaging, 1 year after diagnosis.
DISCUSSION Though several reports in the literature exist on unusual presentations of breast cancer, there are several salient lessons to be learned from this case. Lesson 1. Aggressive forms of breast cancer can occur after treatment of noninvasive disease.
FIGURE 2. Skin punch biopsy sites. Metastatic infiltrating ductal carcinoma of breast is found in the right upper back (A), left lower back (C), and left breast. The left posterior back (B) and left posterior shoulder (D) reveal superficial perivascular and periadnexal lymphohistiocytic inflammation.
IBC is uncommon, representing approximately 2.5% of all cases of breast cancer.1,2 IBC occurs in the setting of an aggressive, invasive breast cancer; the diagnosis is mostly clinical, with the hallmark of overlying skin inflammation secondary to lymph channels that are clogged by tumor cells. Our patient sought treatment for the symptoms of her IBC approximately 3.5 years after a lumpectomy for DCIS of the right breast. The presence of multiple foci of infiltrating ductal carcinoma of the right breast at the time of bilateral modified radical mastectomy allows for 1 of 2 possibilities concerning the recurrence of disease. The first possibility is her IBC is the result of evolution of residual DCIS from several years prior. The second possibility is the present IBC is the result of spontaneous occurrence of new disease, to which she was likely at higher risk secondary to her previous DCIS history. Although there is no way to know for certain which is the case for our patient, the duration of the apparent disease-free interval, as evidenced by repeated mammogram and MRI, suggests the latter. Lesson 2. IBC can be difficult to diagnose, as obstructed lymphatics from the tumor can mimic inflammatory diseases or lymphedema. The difficultly in the diagnosis of IBC can result in a delay in diagnosis, as seen in this case. There are several reasons for such a delay in diagnosis to occur. First, IBC is a rare disease entity. Second, obstructed lymphatics from tumor can mimic inflammatory diseases which are more common, such as mastitis. Third, the presence of lymphedema can further obscure the presentation, as it can be easily attributed to other diseases, such as cellulitis; such was the case with our patient. As a result, she was treated first with compression therapy and eventually with multiple antibiotic regimes, which proved to be ineffective. Thus, the delay between her initial presentation and suspicion of IBC was unfortunately 4 months. Given these difficulties, such a delay is not surprising. Nonetheless, published case reports of IBC generally do not mention or discuss any significant delay between initial presentation and suspicion of IBC.3-11 Our case demonstrates that a high index of suspicion and knowledge of the patient’s previous breast cancer history is essential. Extremity lymphedema starting 4 years after a breast operation is unusual and should provoke a thorough investigation to find the cause.
Journal of Surgical Education • Volume 69/Number 3 • May/June 2012
351
FIGURE 3. Right breast mammogram before chemotherapy showing calcifications in the right breast suspicious for malignancy, diffuse skin thickening of the right breast, and early skin thickening of the left breast (not shown).
Lesson 3. The treatment of patients with IBC poses unique challenges for which a multimodality approach is often needed. Our patient was treated using a multimodality approach consisting of neoadjuvant chemotherapy, surgery, and radiation therapy. Both the breast and skin metastases responded favorably to chemotherapy. This therapy consisted of doxorubicin and cyclophosphamide, followed by paclitaxel. Despite a favorable response with chemotherapy, skin biopsies to confirm absence of tumor in the skin of the back and left breast were performed. Given no cancer was seen, we were more confident that resection would lead to negative margins and the chance of sewing together skin flaps free of IBC. With resolution of FDGavid lesions on imaging studies, an aggressive plan of bilateral mastectomy and radiotherapy was pursued. These therapies were offered in hopes of adding meaningful survival benefit. In
a study from our institution, of 156 patients with nonmetastatic IBC who were treated with some form of multimodal therapy, overall and disease-free 5-year survival was 42% and 21%, respectively.12 Other studies have reported 2-, 10-, and 20-year overall survival rates of 82%, 32%-38%, and 19%, respectively using various regimens.13-16 Although radiotherapy retreatment is common across many types of cancer, median time between retreatment episodes has been observed to be longest in breast cancer (12.5 months).17 As our patient was treated several years prior with radiotherapy for DCIS, the need for repeat radiotherapy adds complexity to her care. Analysis of the clinical outcomes of repeat radiation treatments in patients with recurrent breast cancer have been the topic of investigations in multiple recent studies.18-20 Furthermore, these studies have sought to understand the late-occurring
FIGURE 4. Positron emission tomography (PET) scans demonstrating resolution of increased fluorodeoxyglucose (FDG) uptake, before (A and C) and after (B and D) chemotherapy. 352
Journal of Surgical Education • Volume 69/Number 3 • May/June 2012
FIGURE 5. Four weeks after bilateral modified radical mastectomy.
toxicity effects of repeated breast irradiation, including lymphedema, dermatitis, fibrosis, necrosis, and telangiectasia. Although there is substantial patient variation between and within studies (time between radiotherapy treatments, total radiation dose, age at diagnosis, chemotherapeutic status, etc), several important observations can be related to our patient. Specifically, the success of repeat radiotherapy in terms of local control and survival is largely dependent on the presence of gross/macroscopic tumor load.18,20 In general, these studies have found the success of local response rates to outweigh the risk posed by late-occurring toxicity effects. Although these benefits are clearer for patients with locally recurrent breast cancer, repeat radiotherapy appears to also provide acceptable outcomes for patients with distantly recurrent disease, especially when combined with local radio frequency hyperthermia therapy.18,20 Lesson 4. IBC can present with distant and unusual metastases. The presentation of IBC in our patient is unusual because of her distant skin metastases to the back. While there are extensive reviews (and many case reports) regarding the topic of cutaneous metastases from noncutaneous cancers,21-24 and indeed the most common primary source of such metastases appears to be breast adenocarcinoma, distant skin metastases are rare. To our knowledge, there is only 1 existing report of arguably distant cutaneous metastasis of IBC. Przylecki et al.25 reported skin metastases to the upper abdomen in a patient previously treated with chemotherapy, radiation therapy, hormonal therapy, and surgery, including reconstruction, for ductal carcinoma. Lesson 5. IBC is dangerous. In general, the long-term outcome with IBC is poor. Limited data on survival of IBC patients with metastases exists. Hennessy et al.26 reported in a study of metastatic IBC patients treated with primary chemotherapy and surgery, the 5-year overall survival was 82.5% when pathologic complete response of axillary lymph nodes was demonstrated, as compared with 37.1% when it was not. Sutherland et al.27 found that metastatic disease at presentation was found to decrease median survival from 3.9 to 1.7 years. Schairer et al.28 reported that the absolute risk of developing contralateral breast cancer (CBC) after IBC to be 4.9% at 2 years and 7.7% at 20 years. The
contralateral breast cancer risk for a patient with noninflammatory invasive breast cancer is about 0.8% per year.29 Based on these data, the authors argued that early recurrences are likely to be the result of metastatic disease, while later recurrences are likely the result of independent primary cancers. Multiple initial metastases to the back and contralateral breast, along with subsequent presence of metastatic adenocarcinoma in several left axillary lymph nodes postmastectomy suggests that our patient is at high risk for recurrence of disease. However, her positive response to treatment and a physical examination void of any current cutaneous lesions is encouraging.
CONCLUSIONS This report reflects on important lessons to be learned from an interesting case of a patient with IBC. Specifically, this perplexing and complex disease can occur after treatment for prior noninvasive disease. A high index of suspicion and awareness of IBC are crucial to shorten the potential delay in diagnosis that can result from the difficulty of diagnosis. Though prognosis is relatively poor for IBC, multimodality treatment with aggressive medical, surgical, and radiation therapy can achieve reasonable outcomes in selected patients. Finally, although distant skin metastases from IBC are extremely rare and may confer a poor prognosis, we remain guardedly optimistic about the longterm outcome of this upbeat patient.
REFERENCES 1. Hance KW, Anderson WF, Devesa SS, Young HA, Levine
PH. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97:966-975. 2. Robertson FM, Bondy M, Yang W, et al. Inflammatory
Journal of Surgical Education • Volume 69/Number 3 • May/June 2012
breast cancer: the disease, the biology, the treatment. CA Cancer J Clin. 2010;60:351-375. 353
3. Shigematsu H, Nakamura Y, Tanaka K, et al. A case of
inflammatory breast cancer: 20 years of follow-up. Int J Radiat Oncol Biol Phys. 2012;82:690-695.
HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment. Int J Clin Oncol. 2010;15:615-620.
17. Barton MB, Hudson HM, Delaney G, Gruver P, Liu Z.
4. Montagna E, Cancello G, Torrisi R, et al. Lapatinib and
18. Wahl AO, Rademaker A, Kiel KD, et al. Multi-institu-
metronomic capecitabine combination in an HER2-positive inflammatory breast cancer patient: a case report. Ann Oncol. 2010;21:667-668.
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Journal of Surgical Education • Volume 69/Number 3 • May/June 2012