Outcomes in Nonmetastatic Hormone Receptor–Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study

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Ryan Ying Cong Tan Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Duke-NUS Medical School, Singapore

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Whee Sze Ong Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore

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Kyung-Hun Lee Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

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Seri Park Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of South Korea

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Jabed Iqbal Duke-NUS Medical School, Singapore
Division of Pathology, Singapore General Hospital, Singapore

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Yeon Hee Park Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of South Korea
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of South Korea

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Jeong Eon Lee Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of South Korea

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Jong Han Yu Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of South Korea

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Ching-Hung Lin Department of Medical Oncology, National Taiwan University Hospital, Cancer Center Branch, Taipei, Taiwan

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Yen-Shen Lu Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

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Makiko Ono Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

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Takayuki Ueno Breast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

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Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Japan

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Tatsuya Onishi Department of Breast Surgery, National Cancer Center Hospital East, Kashiwa, Japan

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Geok-Hoon Lim Breast Department, KK Women’s and Children’s Hospital, Singapore
SingHealth Duke-NUS Breast Centre, Singapore

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Su-Ming Tan SingHealth Duke-NUS Breast Centre, Singapore
Division of Breast Surgery, Department of General Surgery, Changi General Hospital, Singapore

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Han-Byoel Lee Department of Surgery, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

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Jiwon Koh Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

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Wonshik Han Department of Surgery, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

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Seock-Ah Im Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

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Veronique Kiak Mien Tan Duke-NUS Medical School, Singapore
SingHealth Duke-NUS Breast Centre, Singapore
Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore
Department of Breast Surgery, Singapore General Hospital, Singapore

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Nitar Phyu Department of Cancer Informatics, National Cancer Centre Singapore, Singapore

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Fuh-Yong Wong Duke-NUS Medical School, Singapore
Department of Cancer Informatics, National Cancer Centre Singapore, Singapore
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore

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Puay Hoon Tan Luma Medical Centre, Singapore

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Yoon-Sim Yap Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Duke-NUS Medical School, Singapore

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Background: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. Methods: Individual patient-level data from 6 centers on stage I–III hormone receptor–positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. Results: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43–0.80), RFS (HR, 0.70; 95% CI, 0.56–0.89), and OS (HR, 0.71; 95% CI, 0.53–0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non–breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08–5.40), radiotherapy (HR, 0.44; 95% CI, 0.23–0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09–0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. Conclusions: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

Submitted October 19, 2023; final revision received December 7, 2023; accepted for publication December 11, 2023. Published online May 14, 2024.

Author contributions: Study concept & design: Yap. Data curation: All authors. Formal analysis: Ong. Methodology: R.Y.C. Tan, Ong, Yap. Project administration: Yap. Software: Ong. Writing—original draft: R.Y.C. Tan. Writing—review & editing: All authors.

Data availability statement: The study team is agreeable to share aggregate participant data that underlie the results reported in this Article (after de-identification and establishment of data sharing agreement), upon reasonable request. To gain access, data requestors should submit a request to the corresponding author.

Disclosures: Dr. Y.H. Park has disclosed serving on a data safety monitoring board and on an advisory board for AstraZeneca, Pfizer, Roche, Menarini, Novartis, and Daiichi-Sankyo; and serving as a consultant for AstraZeneca, Pfizer, Lilly, Gilead, Merck & Co., Inc., Eisai, Roche, Daiichi-Sankyo, Menarini, Everest Pharmaceuticals, and Novartis. Dr. Ueno has disclosed receiving grant/research support from Eli Lilly Japan KK. Dr. Koh has disclosed serving as a consultant for DCGEN. Dr. Im has disclosed receiving grant/research support from AstraZeneca, Boryung, Daewoong Pharmaceutical, Daiichi-Sankyo, Eisai, Pfizer, and Roche; and serving on an advisory board and as a consultant for AstraZeneca, Bertis, Daiichi-Sankyo, Eisai, GSK, Hanmi Pharmaceutical, Idience, Lilly, MSD, Novartis, Pfizer, and Roche. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was supported by the Singapore National Medical Research Council (MOH-CSAINV18nov-0009; Y.S. Yap).

Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2023.7121. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.

Correspondence: Yoon-Sim Yap, MBBS, PhD, Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore 168583. Email: gmsyapys@nus.edu.sg

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  • 1.

    Di Saverio S, Gutierrez J, Avisar E. A retrospective review with long term follow up of 11,400 cases of pure mucinous breast carcinoma. Breast Cancer Res Treat 2008;111:541547.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Kim J, Kim JY, Lee HB, et al. Characteristics and prognosis of 17 special histologic subtypes of invasive breast cancers according to World Health Organization classification: comparative analysis to invasive carcinoma of no special type. Breast Cancer Res Treat 2020;184:527542.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Zhou X, Zheng Z, Li Y, et al. The clinical features and prognosis of patients with mucinous breast carcinoma compared with those with infiltrating ductal carcinoma: a population-based study. BMC Cancer 2021;21:536.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Yap YS. Outcomes in breast cancer—does ethnicity matter? ESMO Open 2023;8:101564.

  • 5.

    Tan PH, Ellis I, Allison K, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology 2020;77:181185.

  • 6.

    Budzik MP, Fudalej MM, Badowska-Kozakiewicz AM. Histopathological analysis of mucinous breast cancer subtypes and comparison with invasive carcinoma of no special type. Sci Rep 2021;11:5770.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Hanagiri T, Ono K, Baba T, et al. Clinicopathologic characteristics of mucinous carcinoma of the breast. Int Surg 2010;95:126129.

  • 8.

    Colleoni M, Rotmensz N, Maisonneuve P, et al. Outcome of special types of luminal breast cancer. Ann Oncol 2012;23:14281436.

  • 9.

    Gradishar WJ, Moran MS, Abraham J, et al. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 4.2023. Accessed December 1, 2023. To view the most recent version, visit https://www.nccn.org

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Kim HS, Lee JU, Yoo TK, et al. Omission of chemotherapy for the treatment of mucinous breast cancer: a nationwide study from the Korean Breast Cancer Society. J Breast Cancer 2019;22:599612.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Gao HF, Li WP, Zhu T, et al. Adjuvant chemotherapy could benefit early-stage ER/PR positive mucinous breast cancer: a SEER-based analysis. Breast 2020;54:7987.

  • 12.

    Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 2010;134:e4872.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 2010;28:27842795.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 2007;131:1843.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 2013;31:39974013.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Wong FY, Wong RX, Zhou S, et al. Effects of housing value and medical subsidy on treatment and outcomes of breast cancer patients in Singapore: a retrospective cohort study. Lancet Reg Health West Pac 2020;6:100065.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    American Cancer Society; Fleming ID, Cooper JS, Henson DE, et al., eds. AJCC Cancer Staging Manual, 5th ed. Springer; 1997.

  • 18.

    American Cancer Society; Greene FL, Page DL, Fleming ID, et al., eds. AJCC Cancer Staging Manual, 6th ed. Springer; 2002.

  • 19.

    American Cancer Society; Edge SB, Byrd DR, Compton CC, et al., eds. AJCC Cancer Staging Manual, 7th ed. Springer; 2010.

  • 20.

    Tolaney SM, Garrett-Mayer E, White J, et al. Updated standardized definitions for efficacy end points (STEEP) in adjuvant breast cancer clinical trials: STEEP version 2.0. J Clin Oncol 2021;39:27202731.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Pareja F, Lee JY, Brown DN, et al. The genomic landscape of mucinous breast cancer. J Natl Cancer Inst 2019;111:737741.

  • 22.

    Nguyen B, Veys I, Leduc S, et al. Genomic, transcriptomic, epigenetic, and immune profiling of mucinous breast cancer. J Natl Cancer Inst 2019;111:742746.

  • 23.

    Yim HE, Kim JH, Ahn MS, et al. Clinicopathological and molecular analysis of 45 cases of pure mucinous breast cancer. Front Oncol 2021;10:558760.

  • 24.

    Nguyen B, Sanchez-Vega F, Fong CJ, et al. The genomic landscape of carcinomas with mucinous differentiation. Sci Rep 2021;11:9478.

  • 25.

    Zhu X, Li Y, Liu F, et al. Construction of a prognostic nomogram model for patients with mucinous breast cancer. J Healthc Eng 2022;2022:1230812.

  • 26.

    Gao T, Chen Y, Li M, et al. Nomogram for predicting survival in patients with mucinous breast cancer undergoing chemotherapy and surgery: a population-based study. Eur J Med Res 2023;28:415.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Wang J, He ZY, Dong Y, et al. The distribution and outcomes of the 21-gene recurrence score in T1-T2N0 estrogen receptor-positive breast cancer with different histologic subtypes. Front Genet 2018;9:638.

    • PubMed
    • Search Google Scholar
    • Export Citation

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