Preoperative concurrent endocrine therapy with chemotherapy in luminal B-like breast cancer

Breast Cancer volume 27, pages819–827(2020)Cite this article

Abstract

Purpose

Luminal B-like breast cancer is sensitive to both chemotherapy and endocrine therapy. We aimed to assess the safety and efficacy of concomitant chemotherapy and endocrine therapy compared with chemotherapy alone in the preoperative setting in luminal B-like breast cancer.

Methods

This two-arm randomized clinical trial enrolled patients with luminal B-like human epithelial growth factor 2-negative breast cancer, who were randomly assigned at a 1:1 ratio to receive preoperative chemotherapy alone or preoperative endocrine therapy concurrent with chemotherapy for 24 weeks before surgery. The primary endpoint was the pathological complete response (pCR) rate. The secondary endpoints included the clinical response rate, toxicity, and health-related quality of life (HRQOL).

Results

Overall, 70 patients were randomly assigned to the chemotherapy and chemo-endocrine therapy groups. The pCR rates were 9.7% and 3.0% (P = 0.319), and the clinical complete response rates were 5.9% and 5.6% (P = 0.745) in the chemotherapy and chemo-endocrine therapy groups, respectively. There were no clear differences in treatment-related adverse events or HRQOL between the two groups.

Conclusions

In patients with luminal B-like breast cancer, the pCR, clinical response rate, toxicity, and HRQOL with the concomitant administration of endocrine therapy and chemotherapy were not superior to chemotherapy alone in the preoperative setting.

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Data availability

The data sets generated during or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ER:

Estrogen receptor

PgR:

Progesterone receptor

HER-2:

Human epithelial growth factor-2

pCR:

Pathological complete response

HRQOL:

Health-related quality of life

FACT-G:

Functional Assessment of Cancer Therapy-General

FACT-B:

Functional Assessment of Cancer Therapy-Breast

FACT-ES:

Functional Assessment of Cancer Therapy-Endocrine Subscale

HADS:

Hospital Anxiety and Depression Scale

References

  1. 1.

    Colleoni M, Montagna E. Neoadjuvant therapy for ER-positive breast cancers. Ann Oncol. 2012;23(Suppl 10):x243–x248248.

    Article  Google Scholar 

  2. 2.

    Seo JH, Kim YH, Kim JS. Meta-analysis of pre-operative aromatase inhibitor versus tamoxifen in postmenopausal woman with hormone receptor-positive breast cancer. Cancer Chemother Pharmacol. 2009;63:261–6.

    CAS  Article  Google Scholar 

  3. 3.

    Reinert T, Ramalho S, Goncalves R, Barrios CH, Graudenz MS, Bines J. Multidisciplinary approach to neoadjuvant endocrine therapy in breast cancer: a comprehensive review. Rev Bras Ginecol Obstet. 2016;38:615–22.

    Article  Google Scholar 

  4. 4.

    Colleoni M, Viale G, Zahrieh D, Pruneri G, Gentilini O, Veronesi P, et al. Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin Cancer Res. 2004;10:6622–8.

    CAS  Article  Google Scholar 

  5. 5.

    Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24:1037–44.

    Article  Google Scholar 

  6. 6.

    Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432–44.

    CAS  Article  Google Scholar 

  7. 7.

    Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160–7.

    Article  Google Scholar 

  8. 8.

    Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.

    CAS  Article  Google Scholar 

  9. 9.

    von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.

    Article  Google Scholar 

  10. 10.

    Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.

    Article  Google Scholar 

  11. 11.

    Mohammadianpanah M, Ashouri Y, Hoseini S, Amadloo N, Talei A, Tahmasebi S, et al. The efficacy and safety of neoadjuvant chemotherapy +/− letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial. Breast Cancer Res Treat. 2011;132:853–61.

    Article  Google Scholar 

  12. 12.

    Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. 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. 2001;2001(30):96–102.

    Article  Google Scholar 

  13. 13.

    Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165–74.

    CAS  Article  Google Scholar 

  14. 14.

    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22:1736–47.

    CAS  Article  Google Scholar 

  15. 15.

    Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, et al. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012;13:345–52.

    CAS  Article  Google Scholar 

  16. 16.

    Kurosumi M, Akashi-Tanaka S, Akiyama F, Komoike Y, Mukai H, Nakamura S, et al. Histopathological criteria for assessment of therapeutic response in breast cancer (2007 version). Breast Cancer. 2008;15:5–7.

    Article  Google Scholar 

  17. 17.

    Fallowfield LJ, Leaity SK, Howell A, Benson S, Cella D. Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT-B. Breast Cancer Res Treat. 1999;55:189–99.

    CAS  Article  Google Scholar 

  18. 18.

    Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, et al. The Functional Assessment of Cancer Therapy Scale: development and validation of the general measure. J Clin Oncol. 1993;11:570–9.

    CAS  Article  Google Scholar 

  19. 19.

    Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, et al. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument. J Clin Oncol. 1997;15:974–86.

    CAS  Article  Google Scholar 

  20. 20.

    Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 1983;67:361–70.

    CAS  Article  Google Scholar 

  21. 21.

    Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007;110:244–54.

    CAS  Article  Google Scholar 

  22. 22.

    Palmieri C, Cleator S, Kilburn LS, Kim SB, Ahn SH, Beresford M, et al. NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer. Breast Cancer Res Treat. 2014;148:581–90.

    CAS  Article  Google Scholar 

  23. 23.

    Alba E, Calvo L, Albanell J, De la Haba JR, Arcusa Lanza A, Chacon JI, et al. Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study. Ann Oncol. 2012;23:3069–74.

    CAS  Article  Google Scholar 

  24. 24.

    Montagna E, Bagnardi V, Viale G, Rotmensz N, Sporchia A, Cancello G, et al. Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy. Ann Oncol. 2015;26:307–13.

    CAS  Article  Google Scholar 

  25. 25.

    Gnant M, Harbeck N, Thomssen CS, Gallen V. A brief summary of the consensus discussion about escalation and de-escalation of primary breast cancer treatment. Breast Care (Basel). 2017;2017(12):102–7.

    Article  Google Scholar 

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Acknowledgements

We thank Dr. Yuji Tokunaga, Dr. Tomomi Hayashi, Dr. Yuko Hosokawa, Dr. Yumiko Taki, Dr. Hirofumi Fujita, Dr. Hiromi Jotoku, Dr. Megumi Takehara, Dr. Junpei Tochikubo, Dr. Takachika Ozawa, Dr. Hanae Suzuki, and Mr. Yasunori Miyamoto for their kind cooperation. We also thank the patients who were treated with this protocol and their families.

Funding

The authors declare that this study was not funded.

Author information

Affiliations

  1. First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, 431-3192, Japan

    Ryoichi Matsunuma, Kei Koizumi, Hiroyuki Ogura & Norihiko Shiiya

  2. Department of Breast Surgery, Shizuoka General Hospital, Shizuoka, Shizuoka, 420-8527, Japan

    Ryoichi Matsunuma

  3. Department of Medical Oncology, Hamamatsu Oncology Center, Hamamatsu, Shizuoka, 430-0929, Japan

    Toru Watanabe & Noriko Sawai

  4. Department of Breast Surgery, Jichi Medical University Hospital, Shimotsuke, Tochigi, 329-0498, Japan

    Yasuo Hozumi

  5. Department of Breast Surgery, University of Tsukuba Hospital/Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, 309-1793, Japan

    Yasuo Hozumi

  6. Department of Breast Surgery, Iwata City Hospital, Iwata, Shizuoka, 438-8550, Japan

    Yasushi Ito & Keigo Goto

  7. Department of Surgery, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, 433-8558, Japan

    Shoko Maruyama

  8. Department of Breast Surgery, Hamamatsu Medical Center, Hamamatsu, Shizuoka, 432-8580, Japan

    Hiroki Mori

Authors
  1. Ryoichi Matsunuma
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  2. Toru Watanabe
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  3. Yasuo Hozumi
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  4. Kei Koizumi
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  5. Yasushi Ito
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  6. Shoko Maruyama
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  7. Hiroyuki Ogura
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  8. Keigo Goto
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  9. Hiroki Mori
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  10. Noriko Sawai
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  11. Norihiko Shiiya
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Contributions

RM wrote the main manuscript text and TW contributed to study design. RM, TW, YH, KK, YI, SM, HO, KG, HM, and NS contributed to provision of study patients and data collection. All authors reviewed the manuscript.

Corresponding author

Correspondence to Ryoichi Matsunuma.

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Conflict of interest

Ryoichi Matsunuma, Toru Watanabe, Yasuo Hozumi, Yasushi Ito, Shoko Maruyama, Hiroyuki Ogura, Keigo Goto, Hiroki Mori, Noriko Sawai, and Norihiko Shiiya declare that they have no conflict of interest to declare. Kei Koizumi reports personal fees from Pfizer.

Ethical approval

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.

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Informed consent was obtained from all individual participants included in the study.

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Matsunuma, R., Watanabe, T., Hozumi, Y. et al. Preoperative concurrent endocrine therapy with chemotherapy in luminal B-like breast cancer. Breast Cancer 27, 819–827 (2020). https://doi.org/10.1007/s12282-020-01077-0

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Keywords

  • Primary systemic chemotherapy
  • Neoadjuvant chemotherapy
  • Concurrent endocrine therapy
  • Luminal B
  • Chemo-endocrine therapy