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The Effect of Age on Outcomes After Neoadjuvant Chemotherapy for Breast Cancer

Abstract

Background

Younger women (age ≤ 40 years) with breast cancer undergoing neoadjuvant chemotherapy (NAC) have higher rates of pathologic complete response (pCR); however, it is unknown whether axillary or breast downstaging rates differ by age. In this study, we compared pCR incidence and surgical downstaging rates of the breast and axilla post NAC, between patients aged ≤ 40, 41–60, and ≥ 61 years.

Methods

We identified 1383 women with stage I–III breast cancer treated with NAC and subsequent surgery from November 2013 to December 2018. pCR and breast/axillary downstaging rates were assessed and compared across age groups.

Results

Younger women were significantly more likely to have ductal histology, poorly differentiated tumors, and BRCA mutations; 35% of tumors were hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–), 36% were HER2-positive (HER2+), and 29% were triple negative (TN), with similar subtype distribution across age groups (p = 0.6). Overall, pCR rates did not differ by age, however among patients with TN tumors (n = 394), younger women had higher pCR rates (52% vs. 35% among those aged 41–60 years and 29% among those aged ≥61 years; p = 0.007) and were more likely to have tumors with high tumor-infiltrating lymphocyte (TIL) concentrations (p < 0.001). Downstaging to breast-conserving surgery (BCS) eligibility post NAC among initially BCS-ineligible patients was similar across age groups; younger women chose BCS less often (p < 0.001). Among cN1 patients (n = 813), 52% of women ≤40 years of age avoided axillary lymph node dissection (ALND) with NAC, versus 39% and 37% in the older groups (p < 0.001).

Conclusions

Younger women undergoing NAC for axillary downstaging were more likely to avoid ALND across all subtypes; however, overall pCR rates did not differ by age. Despite equivalent breast downstaging and BCS eligibility rates across age groups, younger women were less likely to undergo BCS.

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References

  1. Bouchardy C, Fioretta G, Verkooijen HM, et al. Recent increase of breast cancer incidence among women under the age of forty. Br J Cancer. 2007;96(11):1743–6.

    CAS  Article  Google Scholar 

  2. Colleoni M, Rotmensz N, Robertson C, et al. Very young women (<35 years) with operable breast cancer: features of disease at presentation. Ann Oncol. 2002;13(2):273–9.

    CAS  Article  Google Scholar 

  3. Kroman N, Jensen MB, Wohlfahrt J, Mouridsen HT, Andersen PK, Melbye M. Factors influencing the effect of age on prognosis in breast cancer: population based study. BMJ. 2000;320(7233):474–8.

    CAS  Article  Google Scholar 

  4. Adami HO, Malker B, Holmberg L, Persson I, Stone B. The relation between survival and age at diagnosis in breast cancer. N Engl J Med. 1986;315(9):559–63.

    CAS  Article  Google Scholar 

  5. Anders CK, Hsu DS, Broadwater G, et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008;26(20):3324–30.

    Article  Google Scholar 

  6. Loibl S, Jackisch C, Lederer B, et al. Outcome after neoadjuvant chemotherapy in young breast cancer patients: a pooled analysis of individual patient data from eight prospectively randomized controlled trials. Breast Cancer Res Treat. 2015;152(2):377–87.

    CAS  Article  Google Scholar 

  7. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.

    Article  Google Scholar 

  8. Amin MB, Edge S, Greene F, et al editors. AJCC Cancer Staging Manual. 8th edn. New York, NY: Springer International Publishing; 2017.

    Google Scholar 

  9. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update. Arch Pathol Lab Med. 2020;144(5):545–63.

    CAS  Article  Google Scholar 

  10. Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105–22.

    CAS  Article  Google Scholar 

  11. Dieci MV, Radosevic-Robin N, Fineberg S, et al. Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. Semin Cancer Biol. 2018;52(Pt 2):16–25.

    Article  Google Scholar 

  12. Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–71.

    CAS  Article  Google Scholar 

  13. Boileau JF, Poirier B, Basik M, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol. 2015;33(3):258–64.

    Article  Google Scholar 

  14. Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310(14):1455–61.

    CAS  Article  Google Scholar 

  15. Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14(7):609–18.

    Article  Google Scholar 

  16. Montagna G, Mamtani A, Knezevic A, Brogi E, Barrio AV, Morrow M. Selecting Node-Positive Patients for Axillary Downstaging with Neoadjuvant Chemotherapy. Ann Surg Oncol. 2020;27(11):4515–22.

    Article  Google Scholar 

  17. Gentile LF, Plitas G, Zabor EC, Stempel M, Morrow M, Barrio AV. Tumor Biology Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients Presenting with Locally Advanced Breast Cancer. Ann Surg Oncol. 2017;24(13):3896–902.

    Article  Google Scholar 

  18. Villarreal-Garza C, Bargallo-Rocha JE, Soto-Perez-de-Celis E, et al. Real-world outcomes in young women with breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2016;157(2):385–94.

    CAS  Article  Google Scholar 

  19. Boughey JC, McCall LM, Ballman KV, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg. 2014;260(4):608–614; discussion 614-606.

  20. von Minckwitz G, Untch M, Blohmer JU, 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(15):1796–804.

    Article  Google Scholar 

  21. Copson ER, Maishman TC, Tapper WJ, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol. 2018;19(2):169–80.

    CAS  Article  Google Scholar 

  22. Rosenberg SM, Ruddy KJ, Tamimi RM, et al. BRCA1 and BRCA2 Mutation Testing in Young Women With Breast Cancer. JAMA Oncol. 2016;2(6):730–6.

    Article  Google Scholar 

  23. Couch FJ, Hart SN, Sharma P, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. 2015;33(4):304–11.

    CAS  Article  Google Scholar 

  24. Fasching PA, Loibl S, Hu C, et al. BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study. J Clin Oncol. 2018;36(22):2281–7.

    CAS  Article  Google Scholar 

  25. Hahnen E, Lederer B, Hauke J, et al. Germline Mutation Status, Pathological Complete Response, and Disease-Free Survival in Triple-Negative Breast Cancer: Secondary Analysis of the GeparSixto Randomized Clinical Trial. JAMA Oncol. 2017;3(10):1378–85.

    Article  Google Scholar 

  26. Wunderle M, Gass P, Häberle L, et al. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients. Breast Cancer Res Treat. 2018;171(1):85–94.

    CAS  Article  Google Scholar 

  27. Denkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.

    Article  Google Scholar 

  28. Gao G, Wang Z, Qu X, Zhang Z. Prognostic value of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer: a systematic review and meta-analysis. BMC Cancer. 2020;20(1):179.

    CAS  Article  Google Scholar 

  29. Loi S, Drubay D, Adams S, et al. Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers. J Clin Oncol. 2019;37(7):559–69.

    Article  Google Scholar 

  30. Golshan M, Cirrincione CT, Sikov WM, et al. 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. 2015;262(3):434–439; discussion 438-439.

  31. Golshan M, Cirrincione CT, Sikov WM, et al. 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. 2016;160(2):297–304.

    CAS  Article  Google Scholar 

  32. Golshan M, Loibl S, Wong SM, et al. Breast Conservation After Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Surgical Results From the BrighTNess Randomized Clinical Trial. JAMA Surg. 2020;155(3):e195410.

    Article  Google Scholar 

  33. Petruolo O, Sevilimedu V, Montagna G, Le T, Morrow M, Barrio AV. How often does modern neoadjuvant chemotherapy downstage patients to breast-conserving surgery? Ann Surg Oncol. 2021;28(1):287–94.

    Article  Google Scholar 

  34. Kim HJ, Dominici L, Rosenberg SM, et al. Surgical Treatment after Neoadjuvant Systemic Therapy in Young Women with Breast Cancer: Results from a Prospective Cohort Study. Ann Surg. Epub 23 Dec 2020. https://doi.org/10.1097/SLA.0000000000004296

  35. Criscitiello C, Curigliano G, Burstein HJ, et al. Breast conservation following neoadjuvant therapy for breast cancer in the modern era: Are we losing the opportunity? Eur J Surg Oncol. 2016;42(12):1780–6.

    CAS  Article  Google Scholar 

  36. de Boniface J, Szulkin R, Johansson ALV. Survival After Breast Conservation vs Mastectomy Adjusted for Comorbidity and Socioeconomic Status: A Swedish National 6-Year Follow-up of 48 986 Women. JAMA Surg. 2021;156(7):628–37.

    Article  Google Scholar 

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Correspondence to Audree B. Tadros MD.

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Conflict of interest

Conflict of interest All authors declared no conflict of interest.

Disclosures

The preparation of this study was supported in part by NIH/NCI Cancer Center Support Grant No. P30 CA008748 to Memorial Sloan Kettering Cancer Center. The study was presented in virtual poster format at the 22nd Annual Meeting of the American Society of Breast Surgeons, 29 April–2 May 2021. Monica Morrow has received honoraria from Exact Sciences and Roche, and Hong Zhang is a Consultant to Genentech/Roche and has received payment for consultation work. Francys C. Verdial, Anita Mamtani, Kate R. Pawloski, Varadan Sevilimedu, Timothy M. D’Alfonso, Mary L. Gemignani, Andrea V. Barrio, and Audree B. Tadros have no conflicts of interest to report.

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Verdial, F.C., Mamtani, A., Pawloski, K.R. et al. The Effect of Age on Outcomes After Neoadjuvant Chemotherapy for Breast Cancer. Ann Surg Oncol 29, 3810–3819 (2022). https://doi.org/10.1245/s10434-022-11367-w

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  • DOI: https://doi.org/10.1245/s10434-022-11367-w

Keywords

  • Breast Cancer
  • Neoadjuvant chemotherapy
  • Young women
  • Breast cancer subtypes
  • pCR