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


Journal

Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840

Informations de publication

Date de publication:
Jun 2022
Historique:
received: 12 11 2021
accepted: 10 01 2022
pubmed: 6 3 2022
medline: 11 5 2022
entrez: 5 3 2022
Statut: ppublish

Résumé

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. 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. 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). 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

pubmed: 35246810
doi: 10.1245/s10434-022-11367-w
pii: 10.1245/s10434-022-11367-w
doi:

Substances chimiques

Receptor, ErbB-2 EC 2.7.10.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3810-3819

Subventions

Organisme : NIH/NCI Cancer Center Support Grant
ID : P30CA008748

Informations de copyright

© 2022. Society of Surgical Oncology.

Références

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.
doi: 10.1038/sj.bjc.6603783
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.
doi: 10.1093/annonc/mdf039
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.
doi: 10.1136/bmj.320.7233.474
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.
doi: 10.1056/NEJM198608283150906
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.
doi: 10.1200/JCO.2007.14.2471
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.
doi: 10.1007/s10549-015-3479-z
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.
doi: 10.1016/S0140-6736(13)62422-8
Amin MB, Edge S, Greene F, et al editors. AJCC Cancer Staging Manual. 8th edn. New York, NY: Springer International Publishing; 2017.
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.
doi: 10.5858/arpa.2019-0904-SA
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.
doi: 10.1200/JCO.2018.77.8738
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.
doi: 10.1016/j.semcancer.2017.10.003
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.
doi: 10.1093/annonc/mdu450
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.
doi: 10.1200/JCO.2014.55.7827
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.
doi: 10.1001/jama.2013.278932
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.
doi: 10.1016/S1470-2045(13)70166-9
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.
doi: 10.1245/s10434-020-08650-z
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.
doi: 10.1245/s10434-017-6085-y
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.
doi: 10.1007/s10549-016-3811-2
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.
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.
doi: 10.1200/JCO.2011.38.8595
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.
doi: 10.1016/S1470-2045(17)30891-4
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.
doi: 10.1001/jamaoncol.2015.5941
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.
doi: 10.1200/JCO.2014.57.1414
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.
doi: 10.1200/JCO.2017.77.2285
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.
doi: 10.1001/jamaoncol.2017.1007
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.
doi: 10.1007/s10549-018-4797-8
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.
doi: 10.1016/S1470-2045(17)30904-X
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.
doi: 10.1186/s12885-020-6668-z
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.
doi: 10.1200/JCO.18.01010
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.
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.
doi: 10.1007/s10549-016-4006-6
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.
doi: 10.1001/jamasurg.2019.5410
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.
doi: 10.1245/s10434-020-08593-5
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
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.
doi: 10.1016/j.ejso.2016.10.011
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.
doi: 10.1001/jamasurg.2021.1438

Auteurs

Francys C Verdial (FC)

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Anita Mamtani (A)

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Kate R Pawloski (KR)

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Varadan Sevilimedu (V)

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Timothy M D'Alfonso (TM)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Hong Zhang (H)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Mary L Gemignani (ML)

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Andrea V Barrio (AV)

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Monica Morrow (M)

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Audree B Tadros (AB)

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. tadrosa@mskcc.org.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH