Abstract
Purpose
We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer.
Methods
A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC.
Results
Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30–0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32–0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09–0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09–0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24–1.22) while that for OS was 0.98 (95% CI 0.46–1.84) for MedBC.
Conclusion
In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.
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References
Ridolfi RL, Rosen PP, Port A, Kinne D, Mike V (1977) Medullary carcinoma of the breast: a clinicopathologic study with 10 year follow-up. Cancer 40:1365–1385. https://doi.org/10.1002/1097-0142(197710)40:4%3c1365::aid-cncr2820400402%3e3.0.co;2-n
Park I, Kim J, Kim M, Bae SY, Lee SK, Kil WH, Lee JE, Nam SJ (2013) Comparison of the characteristics of medullary breast carcinoma and invasive ductal carcinoma. J Breast Cancer 16:417–425. https://doi.org/10.4048/jbc.2013.16.4.417
Huober J, Gelber S, Goldhirsch A, Coates AS, Viale G, Ohlschlegel C, Price KN, Gelber RD, Regan MM, Thurlimann B (2012) Prognosis of medullary breast cancer: analysis of 13 international breast cancer study group (IBCSG) trials. Ann Oncol 23:2843–2851. https://doi.org/10.1093/annonc/mds105
Dai D, Shi R, Wang Z, Zhong Y, Shin VY, Jin H, Wang X (2020) Competing risk analyses of medullary carcinoma of breast in comparison to infiltrating ductal carcinoma. Sci Rep 10:560. https://doi.org/10.1038/s41598-019-57168-2
Vo T, Xing Y, Meric-Bernstam F, Mirza N, Vlastos G, Symmans WF, Perkins GH, Buchholz TA, Babiera GV, Kuerer HM, Bedrosian I, Akins JS, Hunt KK (2007) Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy. Am J Surg 194:527–531. https://doi.org/10.1016/j.amjsurg.2007.06.012
Ellis IO, Galea M, Broughton N, Locker A, Blamey RW, Elston CW (1992) Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology 20:479–489. https://doi.org/10.1111/j.1365-2559.1992.tb01032.x
Wang XX, Jiang YZ, Liu XY, Li JJ, Song CG, Shao ZM (2016) Difference in characteristics and outcomes between medullary breast carcinoma and invasive ductal carcinoma: a population based study from SEER 18 database. Oncotarget 7:22665–22673. https://doi.org/10.18632/oncotarget.8142
Mateo AM, Pezzi TA, Sundermeyer M, Kelley CA, Klimberg VS, Pezzi CM (2017) Chemotherapy significantly improves survival for patients with T1c–T2N0M0 medullary breast cancer: 3739 cases from the national cancer data base. Ann Surg Oncol 24:1050–1056. https://doi.org/10.1245/s10434-016-5649-6
Lim S, Park SH, Park HK, Hur MH, Oh SJ, Suh YJ (2015) Prognostic role of adjuvant chemotherapy in node-negative (N0), triple-negative (TN), medullary breast cancer (MBC) in the Korean population. PLoS ONE 10:e0140208. https://doi.org/10.1371/journal.pone.0140208
Trapani D, Giugliano F, Uliano J, Zia VAA, Marra A, Viale G, Ferraro E, Esposito A, Criscitiello C, D’amico P, Curigliano G (2021) Benefit of adjuvant chemotherapy in patients with special histology subtypes of triple-negative breast cancer: a systematic review. Breast Cancer Res Treat 187:323–337. https://doi.org/10.1007/s10549-021-06259-8
Kubo M, Kumamaru H, Isozumi U, Miyashita M, Nagahashi M, Kadoya T, Kojima Y, Aogi K, Hayashi N, Tamura K, Asaga S, Niikura N, Ogo E, Iijima K, Tanakura K, Yoshida M, Miyata H, Yamamoto Y, Imoto S, Jinno H (2020) Annual report of the Japanese breast cancer society registry for 2016. Breast Cancer 27:511–518. https://doi.org/10.1007/s12282-020-01081-4
Miyata H, Gotoh M, Hashimoto H, Motomura N, Murakami A, Tomotaki A, Hirahara N, Ono M, Ko C, Iwanaka T (2014) Challenges and prospects of a clinical database linked to the board certification system. Surg Today 44:1991–1999. https://doi.org/10.1007/s00595-013-0802-3
Tsiatis AA (2006) Semiparametric theory and missing data. Springer, New York
Doove LL, Van Buuren S, Dusseldorp E (2014) Recursive partitioning for missing data imputation in the presence of interaction effects. Comput Stat Data Anal 72:92–104. https://doi.org/10.1016/j.csda.2013.10.025
Steenbruggen TG, van Werkhoven E, van Ramshorst MS, Dezentjé VO, Kok M, Linn SC, Siesling S, Sonke GS (2020) Adjuvant chemotherapy in small node-negative triple-negative breast cancer. Eur J Cancer 135:66–74
Gradishar WJ, Moran MS, Abraham J, Aft R, Agnese D, Allison KH, Blair SL, Burstein HJ, Dang C, Elias AD, Giordano SH, Goetz MP, Goldstein LJ, Hurvitz SA, Isakoff SJ, Jankowitz RC, Javid SH, Krishnamurthy J, Leitch M, Lyons J, Matro J, Mayer IA, Mortimer J, O'Regan RM, Patel SA, Pierce LJ, Rugo HS, Sitapati A, Smith KL, Smith ML, Soliman H, Stringer-Reasor EM, Telli ML, Ward JH, Wisinski KB, Young JS, Burns JL, Kumar R (2021) NCCN guidelines® insights: breast cancer, version 4.2021
Tokuda Y, Kumamaru H, Jinno H (2019) The Japanese breast cancer society breast cancer registry in the national clinical database: current status and future perspectives to improve outcomes for breast cancer patients. J Jpn Surg Soc 120:639–645 (in Japanese)
Acknowledgements
We thank the affiliated institutes participating in the Japanese Breast Cancer Registry of the JBCS for their efforts to register patients’ data. We thank the Japanese Breast Cancer Society for their grant support to perform the present study.
Funding
This work was supported by the Japanese Breast Cancer Society.
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The study was designed by TA, HK, MI, and MM. All data were analyzed by HK, HM, YT and interpreted by all authors. SI and HJ contributed to funding acquisition and supervision. TA, MI, and MM drafted the manuscript. All authors listed, critically reviewed, and approved the manuscript before submission.
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HK reports receiving speaker fees from Chugai Pharmaceutical Co., Ltd and Johnson and Johnson KK, and consultation fees from Mitsubishi Tanabe Pharma and EP Croit Co., Ltd. HK is affiliated with the department of Healthcare Quality Assessment at the University of Tokyo. The department is a social collaboration department supported by National Clinical Database, Johnson and Johnson KK, Nipro corporation and Intuitive Sàrl. YT reports receiving consultant fees from Pharmaceuticals and Medical Devices Agency and EPARK, Inc., and lecture fees from SAS Institute Japan Ltd. YT and HK are conducting a collaborative study with Pfizer inc., which is not related to the topic of this study.
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This is a database study. The use of the data for retrospective observational studies was approved by the ethics committee of National Clinical Database, and the Ethics Review Committee at the JBCS approved the study.
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Aihara, T., Kumamaru, H., Ishitobi, M. et al. Prognosis and effectiveness of chemotherapy for medullary breast carcinoma. Breast Cancer Res Treat 196, 635–645 (2022). https://doi.org/10.1007/s10549-022-06749-3
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DOI: https://doi.org/10.1007/s10549-022-06749-3