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Metaplastic breast cancer has a poor response to neoadjuvant systemic therapy

Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Objective

Metaplastic breast cancer (MetaBC) is a rare breast cancer subtype poorly responsive to systemic therapy in the metastatic setting with high recurrence rates in the adjuvant setting. However, limited data exist regarding response to neoadjuvant chemotherapy (NAC). We performed a single institutional study to assess the clinical and pathological complete response rates (pCR) of MetaBC to NAC.

Methods

Mayo Clinic Rochester patients with MetaBC treated with NAC were identified using the institutional medical index. Patient demographics, tumor characteristics, chemotherapy treatment, clinical and pathological response, and long-term outcomes were reviewed. Pathologic response was assessed by direct pathology review (n = 14) or review of outside surgical and pathology reports (n = 4).

Results

Women with MetaBC (n = 18) received NAC from January 1991 to June 2014. The mean age was 50 years (range 33–79) with a mean tumor size of 5.1 cm (range 2.3–11 cm) and 6/18 had pathologically confirmed lymph nodes prior to surgery. The majority (13/18; 72%) were estrogen receptor (ER), progesterone receptor (PR) and HER-2 negative (TNBC), and 1/18 (5.5%) was HER-2 positive. Five had BRCA testing and 2/5 were BRCA-2 positive. The chemotherapy regimens included anthracycline/cyclophosphamide (AC) (n = 1), AC/taxane (n = 3), AC/taxane/platinum (n = 8), taxane/platinum-based regimens (n = 4), taxane/cyclophosphamide (n = 1) and taxane/trastuzumab (n = 1). Five of 18 (28%) progressed on initial treatment including two who developed metastatic disease during NAC. The overall pCR rate was 2/18 (11%).

Conclusion

MetaBC is poorly responsive to NAC, with a pCR rate (11%), that is lower than expected in a predominantly TNBC cohort. MetaBC patients should be considered for clinical trials testing new NAC regimens and in the absence of clinical trial enrollment, MetaBC patients with resectable disease should proceed directly to definitive operative management.

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Abbreviations

AC(T):

Adriamycin/cyclophosphamide/(taxane)

BRCA-2:

Breast cancer susceptibility gene-2

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

HER-2:

Human epithelial growth factor-2

IDC:

Invasive ductal carcinoma

KIT:

Stem cell factor receptor

MetaBC:

Metaplastic breast cancer

NAC:

Neoadjuvant chemotherapy

pCR:

Pathologic complete response

PR:

Progesterone receptor

RCB:

Residual Cancer Burden

TNBC:

Triple-negative breast cancer

TP:

Taxane/platinum

TC:

Taxane/cyclophosphamide

References

  1. Pezzi CM, Patel-Parekh L, Cole K, Franko J, Klimberg VS, Bland K (2007) Characteristics and treatment of metaplastic breast cancer: analysis of 892 cases from the National Cancer Database. Ann Surg Oncol 14:166–173. https://doi.org/10.1245/s10434-006-9124-7

    Article  PubMed  Google Scholar 

  2. Rosen PP (2001) Rosen’s breast pathology. Wolters Kluwer, Alphen aan den Rijn

    Google Scholar 

  3. Tavassoli FA (1992) Classification of metaplastic carcinomas of the breast. Pathol Annu 27(Pt 2):89–119

    PubMed  Google Scholar 

  4. Rayson D, Adjei AA, Suman VJ, Wold LE, Ingle JN (1999) Metaplastic breast cancer: prognosis and response to systemic therapy. Ann Oncol 10:413–419

    Article  CAS  PubMed  Google Scholar 

  5. NCCN Clinical Practice Guidelines in Oncology. NCCN

  6. Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B (2001) Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr 30:96–102

    Article  Google Scholar 

  7. Mieog JS, van der Hage JA, van de Velde CJ (2007) Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev 2:CD005002. https://doi.org/10.1002/14651858.cd005002.pub2

    Article  Google Scholar 

  8. Boughey JC, McCall LM, Ballman KV et al (2014) Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer. Ann Surg 260:608–614. https://doi.org/10.1097/sla.0000000000000924 (discussion 614–616)

    Article  PubMed  PubMed Central  Google Scholar 

  9. Al-Hilli Z, Hieken TJ, Hoskin TL, Heins CN, Boughey JC (2015) Impact of neoadjuvant chemotherapy on pathologic axillary nodal status in HER-2 positive patients presenting with clinically node-negative disease. J Surg Oncol 112:453–457. https://doi.org/10.1002/jso.24034

    Article  PubMed  Google Scholar 

  10. Golshan M, Cirrincione CT, Sikov WM et al (2015) Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance). Ann Surg 262:434–439. https://doi.org/10.1097/sla.0000000000001417 (discussion 438–439)

    Article  PubMed  PubMed Central  Google Scholar 

  11. Golshan M, Cirrincione CT, Sikov WM et al (2016) Impact of neoadjuvant therapy on eligibility for and frequency of breast conservation in stage II–III HER2-positive breast cancer: surgical results of CALGB 40601 (Alliance). Breast Cancer Res Treat 160:297–304. https://doi.org/10.1007/s10549-016-4006-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Symmans WF, Peintinger F, Hatzis C et al (2007) Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 25:4414–4422. https://doi.org/10.1200/JCO.2007.10.6823

    Article  PubMed  Google Scholar 

  13. Jung SY, Kim HY, Nam BH et al (2010) Worse prognosis of metaplastic breast cancer patients than other patients with triple-negative breast cancer. Breast Cancer Res Treat 120(627–37):2010. https://doi.org/10.1007/s10549-010-0780-8

    Article  Google Scholar 

  14. Tzanninis IG, Kotteas EA, Ntanasis-Stathopoulos I, Kontogianni P, Fotopoulos G (2016) Management and outcomes in metaplastic breast cancer. Clin Breast Cancer 16:437–443. https://doi.org/10.1016/j.clbc.2016.06.002

    Article  PubMed  Google Scholar 

  15. Gilbert JA, Goetz MP, Reynolds CA et al (2008) Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy. Mol Cancer Ther 7:944–951. https://doi.org/10.1158/1535-7163.MCT-07-0570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374. https://doi.org/10.1158/1078-0432.CCR-04-0220

    Article  CAS  PubMed  Google Scholar 

  17. Reis-Filho JS, Milanezi F, Steele D et al (2006) Metaplastic breast carcinomas are basal-like tumours. Histopathology 49:10–21. https://doi.org/10.1111/j.1365-2559.2006.02467.x

    Article  CAS  PubMed  Google Scholar 

  18. Schwartz TL, Mogal H, Papageorgiou C, Veerapong J, Hsueh EC (2013) Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies. Exp Hematol Oncol 2:31. https://doi.org/10.1186/2162-3619-2-31

    Article  PubMed  PubMed Central  Google Scholar 

  19. Greenup R, Buchanan A, Lorizio W et al (2013) Prevalence of BRCA mutations among women with triple-negative breast cancer (TNBC) in a genetic counseling cohort. Ann Surg Oncol 20:3254–3258. https://doi.org/10.1245/s10434-013-3205-1

    Article  PubMed  Google Scholar 

  20. Sharma P, Klemp JR, Kimler BF et al (2014) Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing. Breast Cancer Res Treat 145:707–714. https://doi.org/10.1007/s10549-014-2980-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nelson RA, Guye ML, Luu T, Lai LL (2015) Survival outcomes of metaplastic breast cancer patients: results from a US population-based analysis. Ann Surg Oncol 22:24–31

    Article  PubMed  Google Scholar 

  22. Song Y, Liu X, Zhang G et al (2013) Unique clinicopathological features of metaplastic breast carcinoma compared with invasive ductal carcinoma and poor prognostic indicators. World J Surg Oncol 11:129. https://doi.org/10.1186/1477-7819-11-129

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lester TR, Hunt KK, Nayeemuddin KM et al (2012) Metaplastic sarcomatoid carcinoma of the breast appears more aggressive than other triple receptor-negative breast cancers. Breast Cancer Res Treat 131:41–48. https://doi.org/10.1007/s10549-011-1393-6

    Article  CAS  PubMed  Google Scholar 

  24. Leon-Ferre RA, Polley MY, Liu H et al (2018) Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer. Breast Cancer Res Treat 167:89–99. https://doi.org/10.1007/s10549-017-4499-7

    Article  CAS  PubMed  Google Scholar 

  25. Hennessy BT, Giordano S, Broglio K et al (2006) Biphasic metaplastic sarcomatoid carcinoma of the breast. Ann Oncol 17:605–613. https://doi.org/10.1093/annonc/mdl006

    Article  CAS  PubMed  Google Scholar 

  26. Leyrer CM, Berriochoa CA, Agrawal S et al (2017) Predictive factors on outcomes in metaplastic breast cancer. Breast Cancer Res Treat 165:499–504. https://doi.org/10.1007/s10549-017-4367-5

    Article  PubMed  Google Scholar 

  27. Ong CT, Campbell BM, Thomas SM et al (2018) Metaplasitc breast cancer treatment and outcomes in 2500 patients: a retrospective analysis of a national onocogy database. Ann Surg Oncol 25:2249–2260. https://doi.org/10.1245/s10434-018-6533-3

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

Supported by Mayo Clinic Breast Specialized Program of Research Excellence Grant No. P50CA116201 (J.N.I. and M.P.G.), Mayo Comprehensive Cancer Center Grant No. P30CA 15083-43 (M.P.G.).

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Authors and Affiliations

Authors

Contributions

ZAH and GC contributed equally to the data collection and interpretation, intellectual content and manuscript preparation. MGK and DWV reviewed pathology slides and assisted with manuscript preparation. JNI, MPG, and JWJ assisted with funding, intellectual content and manuscript preparation.

Corresponding author

Correspondence to James W. Jakub.

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Conflicts of interest

Matthew P. Goetz has consulting or advisory role: Eli Lilly, Novartis, Context Therapeutics, and Sermonix. Research Funding: Eli Lilly, Pfizer. Patents, Royalties, Other Intellectual Property: Methods and Materials for Assessing Chemotherapy Responsiveness and Treating Cancer; Methods and Materials for Using Butyrylcholinesterases to Treat Cancer. The other authors declare they have no competing interests and are in compliance with ethical standard.

Ethics approval

This study was reviewed and approved by Mayo Clinic institutional review board committee under study ID: 14-008981.

Research involving human and animal participants

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 Helsinki Declaration and its later amendments or comparable ethical standards.

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Al-Hilli, Z., Choong, G., Keeney, M.G. et al. Metaplastic breast cancer has a poor response to neoadjuvant systemic therapy. Breast Cancer Res Treat 176, 709–716 (2019). https://doi.org/10.1007/s10549-019-05264-2

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  • DOI: https://doi.org/10.1007/s10549-019-05264-2

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