Top

Discover Oncology

Published in:

Open Access 01-12-2021 | Breast Cancer | Research

The impact of endogenous estrogen exposures on the characteristics and outcomes of estrogen receptor positive, early breast cancer

Authors: Yasmin Korzets, Orly Yariv, Raz Mutai, Assaf Moore, Tzippy Shochat, Rinat Yerushalmi, Hadar Goldvaser

Published in: Discover Oncology | Issue 1/2021

Abstract

Background

Menstrual and parity history might impact the risk for breast cancer. Data on the impact of these factors on other tumor characteristics are limited.

Methods

A single center retrospective cohort study comprising all women with estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative, early breast cancer whose tumors were sent to OncotypeDX analysis. The prespecified subgroups were investigated: age of menarche (< 12 vs. ≥ 12 years), number of deliveries (0 vs. ≥ 1 childbirth and ≥ 5 childbirth vs. other), age of first delivery (≥ 30 years vs. younger age) and postmenopausal compared to premenopausal. The impact of age of menopause was also assessed categorically, using early (< 45 years) and late age of menopause (> 55 years). Differences in tumor characteristics were evaluated using T-test or Mann Whitney for continuous variables or Fisher’s exact test for categorical variables. Outcomes were assessed by Kaplan–Meier survival analysis, with the log-rank test.

Results

A total of 620 women were included. After median follow-up of 10.4 years, early menopause was associated with significantly worse disease-free survival (HR = 2.26, p = 0.004) and overall-survival (HR = 2.60, p = 0.004), and multiparity was associated with significant worse disease-free survival (HR = 2.16, p = 0.026). These differences remain significant in multivariate analyses. Post-menopausal women were more likely to have stronger ER intensity (p = 0.002) but progesterone receptor (PR) positivity was less frequent (p = 0.009(. Early age of menarche was associated with PR positivity (p = 0.039). No other associations were found between the evaluated subgroups and tumor characteristics.

Conclusions

The impact of endogenous estrogen exposure had little effect on breast cancer characteristics of early stage, luminal disease. Early menopause and multiparity were associated with worse outcome.

Available only for authorised users

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. https://doi.org/10.3322/caac.21590.CrossRefPubMed

Key T, Appleby P, Barnes I, Reeves G, Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002;94(8):606–16. https://doi.org/10.1093/jnci/94.8.606.CrossRefPubMed

Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. https://doi.org/10.1093/jnci/dju055.CrossRefPubMedPubMedCentral

Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol. 2012;13(11):1141–51. https://doi.org/10.1016/s1470-2045(12)70425-4.CrossRefPubMedCentral

Ritte R, Lukanova A, Tjønneland A, Olsen A, Overvad K, Mesrine S, et al. Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: a cohort study. Int J Cancer. 2013;132(11):2619–29. https://doi.org/10.1002/ijc.27913.CrossRefPubMed

Nichols HB, Schoemaker MJ, Cai J, Xu J, Wright LB, Brook MN, et al. Breast cancer risk after recent childbirth: a pooled analysis of 15 prospective studies. Ann Intern Med. 2019;170(1):22–30. https://doi.org/10.7326/m18-1323.CrossRefPubMed

Albrektsen G, Heuch I, Hansen S, Kvåle G. Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects. Br J Cancer. 2005;92(1):167–75. https://doi.org/10.1038/sj.bjc.6602302.CrossRefPubMed

Rosner B, Colditz GA, Willett WC. Reproductive risk factors in a prospective study of breast cancer: the Nurses’ Health Study. Am J Epidemiol. 1994;139(8):819–35. https://doi.org/10.1093/oxfordjournals.aje.a117079.CrossRefPubMed

Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, Endogenous Hormones Breast Cancer Collaborative Group, et al. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst. 2003;95(16):1218–26. https://doi.org/10.1093/jnci/djg022.CrossRefPubMed

10.

Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, International Agency for Research on Cancer Handbook Working Group. Body fatness and cancer—viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794–8. https://doi.org/10.1056/nejmsr1606602.CrossRefPubMedPubMedCentral

11.

Missmer SA, Eliassen AH, Barbieri RL, Hankinson SE. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst. 2004;96(24):1856–65. https://doi.org/10.1093/jnci/djh336.CrossRefPubMed

12.

Farhat GN, Cummings SR, Chlebowski RT, Parimi N, Cauley JA, Rohan TE, et al. Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. J Natl Cancer Inst. 2011;103(7):562–70. https://doi.org/10.1093/jnci/djr031.CrossRefPubMedPubMedCentral

13.

Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300. https://doi.org/10.1001/jama.2018.19323.CrossRefPubMed

14.

Sparano JA, Crager MR, Tang G, Gray RJ, Stemmer SM, Shak S. Development and validation of a tool integrating the 21-gene recurrence score and clinical-pathological features to individualize prognosis and prediction of chemotherapy benefit in early breast cancer. J Clin Oncol. 2020;39(6):557–64. https://doi.org/10.1200/JCO.20.03007.CrossRefPubMedPubMedCentral

15.

Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013;139(2):539–52.CrossRefPubMedPubMedCentral

16.

Clark GM, McGuire WL, Hubay CA, Pearson OH, Marshall JS. Progesterone receptors as a prognostic factor in stage II breast cancer. N Engl J Med. 1983;309(22):1343–7. https://doi.org/10.1056/nejm198312013092240.CrossRefPubMed

17.

Lambertini M, Santoro L, Del Mastro L, Nguyen B, Livraghi L, Ugolini D, et al. Reproductive behaviors and risk of developing breast cancer according to tumor subtype: a systematic review and meta-analysis of epidemiological studies. Cancer Treat Rev. 2016;49:65–76. https://doi.org/10.1016/j.ctrv.2016.07.006.CrossRefPubMed

18.

Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111–21. https://doi.org/10.1056/nejmoa1804710.CrossRefPubMedPubMedCentral

19.

Curtit E, Mansi L, Maisonnette-Escot Y, Sautière JL, Pivot X. Prognostic and predictive indicators in early-stage breast cancer and the role of genomic profiling: focus on the Oncotype DX^® Breast Recurrence Score Assay. Eur J Surg Oncol. 2017;43(5):921–30. https://doi.org/10.1016/j.ejso.2016.11.016.CrossRefPubMed

20.

Yang XR, Chang-Claude J, Goode EL, Couch FJ, Nevanlinna H, Milne RL, et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 2011;103(3):250–63. https://doi.org/10.1093/jnci/djq526.CrossRefPubMed

21.

Weidner N, Cote RJ, Suster S, et al. Modern surgical pathology. 2nd ed. Philadelphia: Saunders Elsevier; 2009.

22.

Clemons M, Goss P. Estrogen and the risk of breast cancer. N Engl J Med. 2001;344(4):276–85. https://doi.org/10.1056/nejm200101253440407.CrossRefPubMed

23.

Huang WY, Newman B, Millikan RC, Schell MJ, Hulka BS, Moorman PG. Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status. Am J Epidemiol. 2000;151(7):703–14. https://doi.org/10.1093/oxfordjournals.aje.a010265.CrossRefPubMed

24.

Yoo KY, Tajima K, Miura S, Takeuchi T, Hirose K, Risch H, et al. Breast cancer risk factors according to combined estrogen and progesterone receptor status: a case-control analysis. Am J Epidemiol. 1997;146(4):307–14. https://doi.org/10.1093/oxfordjournals.aje.a009271.CrossRefPubMed

25.

Coyoy A, Guerra-Araiza C, Camacho-Arroyo I. Metabolism regulation by estrogens and their receptors in the central nervous system before and after menopause. Horm Metab Res. 2016;48(8):489–96.CrossRefPubMed

26.

Morselli E, Santos RS, Criollo A, Nelson MD, Palmer BF, Clegg DJ. The effects of oestrogens and their receptors on cardiometabolic health. Nat Rev Endocrinol. 2017;13(6):352–64.CrossRefPubMed

27.

Yang L, Lin L, Kartsonaki C, Guo Y, Chen Y, Bian Z, et al. Menopause characteristics, total reproductive years, and risk of cardiovascular disease among chinese women. Circ Cardiovasc Qual Outcomes. 2017;10(11): e004235. https://doi.org/10.1161/CIRCOUTCOMES.117.004235.CrossRefPubMedPubMedCentral

28.

Ley SH, Li Y, Tobias DK, Manson JE, Rosner B, Hu FB, et al. Duration of reproductive life span, age at menarche, and age at menopause are associated with risk of cardiovascular disease in women. J Am Heart Assoc. 2017;6(11): e006713. https://doi.org/10.1161/JAHA.117.006713.CrossRefPubMedPubMedCentral

29.

Peters SA, Woodward M. Women’s reproductive factors and incident cardiovascular disease in the UK Biobank. Heart. 2018;104(13):1069–75. https://doi.org/10.1136/heartjnl-2017-312289.CrossRefPubMed

30.

Patnaik JL, Byers T, DiGuiseppi C, Dabelea D, Denberg TD. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Res. 2011;13(3):R64.CrossRefPubMedPubMedCentral

31.

Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW. Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA. 2001;285(7):885–92.CrossRefPubMed

32.

Cardoso F, van Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, et al. 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717–29. https://doi.org/10.1056/nejmoa1602253.CrossRefPubMed

33.

Visvanathan K, Fabian CJ, Bantug E, Brewster AM, Davidson NE, DeCensi A, et al. Use of endocrine therapy for breast cancer risk reduction: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(33):3152–65. https://doi.org/10.1200/jco.19.01472.CrossRefPubMed

34.

Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, International Breast Cancer Study Group, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436–46. https://doi.org/10.1056/nejmoa1412379.CrossRefPubMed

35.

Goldvaser H, Barnes TA, Šeruga B, Cescon DW, Ocaña A, Ribnikar D, et al. Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2018;110(1):31–9. https://doi.org/10.1093/jnci/djx141.CrossRef

36.

Amir E, Seruga B, Niraula S, Carlsson L, Ocaña A, et al. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299–309. https://doi.org/10.1093/jnci/djr242.CrossRefPubMed

37.

Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987–98.CrossRefPubMed

38.

Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, et al. Anthracyclines in early breast cancer: the ABC Trials-USOR 06–090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017;35(23):2647–55. https://doi.org/10.1200/JCO.2016.71.4147.CrossRefPubMedPubMedCentral

39.

Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM, PRIME II investigators, et al. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 2015;16(3):266–73. https://doi.org/10.1016/s1470-2045(14)71221-5.CrossRefPubMed

40.

Korzets Y, Fyles A, Shepshelovich D, Amir E, Goldvaser H. Toxicity and clinical outcomes of partial breast irradiation compared to whole breast irradiation for early-stage breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019;175(3):531–45. https://doi.org/10.1007/s10549-019-05209-9.CrossRefPubMed

41.

Sun X, Nichols HB, Tse CK, Bell MB, Robinson WR, Sherman ME, et al. Association of parity and time since last birth with breast cancer prognosis by intrinsic subtype. Cancer Epidemiol Biomark Prev. 2016;25(1):60–7. https://doi.org/10.1158/1055-9965.epi-15-0864.CrossRef

42.

Jääskeläinen A, Roininen N, Karihtala P, Jukkola A. High parity predicts poor outcomes in patients with luminal B-Like (HER2 Negative) early breast cancer: a prospective Finnish Single-Center Study. Front Oncol. 2020;10:1470. https://doi.org/10.3389/fonc.2020.01470.CrossRefPubMedPubMedCentral

43.

Kutty VR, Thankappan KR, Kannan KP, Aravindan KP. How socioeconomic status affects birth and death rates in rural Kerala, India: results of a health study. Int J Health Serv. 1993;23(2):373–86. https://doi.org/10.2190/9N4P-F1L2-13HM-CQVW.CrossRefPubMed

44.

Shawky S, Rashad H, Khadr Z. Reproductive health inequalities in Egypt. Evidence for guiding policies, final report: UNFPA/ASRO. 2018.

45.

Schultz WM, Kelli HM, Varghese T, Shen J, Sandesara P, et al. Socioeconomic status and cardiovascular outcomes: challenges and interventions. Circulation. 2018;137(20):2166–78. https://doi.org/10.1161/CIRCULATIONAHA.117.029652.CrossRefPubMedPubMedCentral

46.

Heliövaara M, Aromaa A. Parity and obesity. J Epidemiol Community Health. 1981;35(3):197–9. https://doi.org/10.1136/jech.35.3.197.CrossRefPubMedPubMedCentral

47.

Hajiahmadi M, Shafi H, Delavar MA. Impact of parity on obesity: a cross-sectional study in Iranian women. Med Princ Pract. 2015n;24(1):70–4. https://doi.org/10.1159/000368358.CrossRefPubMed

48.

Niraula S, Ocana A, Ennis M, Goodwin PJ. Body size and breast cancer prognosis in relation to hormone receptor and menopausal status: a meta-analysis. Breast Cancer Res Treat. 2012;134(2):769–81. https://doi.org/10.1007/s10549-012-2073-x.CrossRefPubMed

49.

Dignam JJ, Wieand K, Johnson KA, Raich P, Anderson SJ, Somkin C, et al. Effects of obesity and race on prognosis in lymph node-negative, estrogen receptor-negative breast cancer. Breast Cancer Res Treat. 2006;97(3):245–54. https://doi.org/10.1007/s10549-005-9118-3.CrossRefPubMed

50.

Schoemaker MJ, Nichols HB, Wright LB, Brook MN, Jones ME, O’Brien KM, Premenopausal Breast Cancer Collaborative Group, et al. Association of body mass index and age with subsequent breast cancer risk in premenopausal women. JAMA Oncol. 2018;4(11):e181771. https://doi.org/10.1001/jamaoncol.2018.1771.CrossRefPubMedPubMedCentral

Title: The impact of endogenous estrogen exposures on the characteristics and outcomes of estrogen receptor positive, early breast cancer
Authors: Yasmin Korzets
Orly Yariv
Raz Mutai
Assaf Moore
Tzippy Shochat
Rinat Yerushalmi
Hadar Goldvaser
Publication date: 01-12-2021
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Estrogens
Published in: Discover Oncology / Issue 1/2021
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-021-00420-x

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Perforated gastric cancer: a critical appraisal

Subcellular localization of HMGB1 in human cholangiocarcinoma: correlation with tumor stage

A genome-wide expression profile of noncoding RNAs in human osteosarcoma cells as they acquire resistance to cisplatin

The gold complex auranofin: new perspectives for cancer therapy

Comprehensive analysis of the MIR4435-2HG/miR-1-3p/MMP9/miR-29-3p/DUXAP8 ceRNA network axis in hepatocellular carcinoma

RETRACTED ARTICLE: IRE1α-XBP1 but not PERK inhibition exerts anti-tumor activity in osteosarcoma

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials