Risk of estrogen receptor–specific breast cancer by family history of estrogen receptor subtypes and other cancers

Q: What was the main objective of the study?

To determine whether the risk of estrogen receptor (ER)–specific breast cancer differs according to the ER status of female first-degree relatives’ breast cancers and whether other first-degree relatives’ cancers are also associated with ER subtypes.

Q: How was the study designed and who was included?

A population-based cohort included 464,707 cancer-free women in Stockholm, Sweden, followed between 1978 and 2019, with analyses stratified by ER-positive and ER-negative breast cancer outcomes.

Q: What did the study find about family history of ER-positive or ER-negative breast cancer?

Women with familial ER-positive breast cancer had higher risk of the ER-positive subtype (HR 1.87), and women with familial ER-negative breast cancer had higher risk of ER-negative subtype (HR 2.54), with risk increasing by number of concordant relatives and younger age at diagnosis.

Sep 24, 2026

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Estrogen receptor (ER)–specific breast cancer risk may vary with the ER subtype of relatives, yet the relationship between ER status in first-degree relatives and ER-specific breast cancer remains insufficiently defined. A population-based cohort of 464,707 cancer-free women in Stockholm (1978–2019) evaluated hazard ratios for ER-positive and ER-negative breast cancer linked to relatives’ ER status and to other first-degree relatives’ cancers. Results showed elevated concordant-subtype risks and increasing risk with more female relatives and younger diagnoses, with nonbreast cancer associations for both ER subtypes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Main Text Background and Rationale

Breast cancer heterogeneity by ER status

Prior family-history evidence and knowledge gap

JNCI: Journal of the National Cancer Institute, 2023, 115(9), 1020–1028 [https://doi.org/10.1093/jnci/djad104](https://doi.org/10.1093/jnci/djad104) Advance Access Publication Date: May 27, 2023 Article Risk of estrogen receptor–specific breast cancer by family history of estrogen receptor subtypes and other cancers Qiao-Li Wang, MD, PhD,1,2 Yuqi Zhang , PhD,1,* Erwei Zeng, PhD,1 Felix Grassmann , PhD,1 Wei He , PhD,1,3,4 Kamila Czene , PhD1 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 2Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 3Chronic Disease Research Institute, The Children’s Hospital, and National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China 4Department of Nutrition and Food Hygiene, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China *Correspondence to: Yuqi Zhang, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels V€ag 12A, 17177 Stockholm, Sweden ([e-mail: yuqi.zhang@ki.se](e-mail: yuqi.zhang@ki.se)) . Abstract Background: The extent to which the risk of estrogen receptor (ER)–speciﬁc breast cancer is associated with ER status of breast cancer and other cancers among ﬁrst-degree relatives is unclear. Methods: This population-based cohort included 464 707 cancer-free women in Stockholm, Sweden, during 1978-2019 . For ERnegative and ER-positive breast cancers, we estimated hazard ratios (HRs) associated with ER status of female ﬁrst-degree relatives with breast cancer and of other cancers in all ﬁrst-degree relatives. Associations between ER-negative and ER-positive status by family cancer history were estimated using logistic regression in a case-only design. Results: Women with familial ER-positive breast cancer had 1.87 times (95% conﬁdence interval [CI] ¼ 1.77 to 1.97) higher risk of ER-positive subtype, whereas the corresponding hazard ratio for ER-negative was 2.54 (95% CI ¼ 2.08 to 3.10) when having familial ER-negative breast cancer. The risk increased with an increasing number of female ﬁrst-degree relatives having concordant subtypes and younger age at diagnosis (Ptrend <.001 for both) . Nonbreast cancers among ﬁrst-degree relatives were associated with both ERpositive (HR ¼ 1.14, 95% CI ¼ 1.10 to 1.17) and ER-negative (HR ¼ 1.08, 95% CI ¼ 1.01 to 1.16) breast cancers. Compared with women with ER-positive breast cancer, women with ER-negative breast cancer were more likely to have family history of liver (odds ratio [OR] ¼ 1.33, 95% CI ¼ 1.05 to 1.67), ovary (OR ¼ 1.28, 95% CI ¼ 1.01 to 1.61), and testicle cancer (OR ¼ 1.79, 95% CI ¼ 1.01 to 3.16) but less likely to have family history of endometrial cancer (OR ¼ 0.77, 95% CI ¼ 0.60 to 1.00) and leukemia (OR ¼ 0.72, 95% CI ¼ 0.56 to 0.91) . Conclusions: Risk of ER-speciﬁc breast cancer differs according to ER status of female ﬁrst-degree relatives with breast cancer and some other cancers of ﬁrst-degree relatives. This family history information should be considered in the individual risk prediction for ER subtypes. Breast cancer is the most common cancer worldwide, and 1 in 8- 10 women is anticipated to be diagnosed with breast cancer during her lifetime (1 ,2) . Breast cancers are heterogenous, and a common way of characterizing tumors is by quantitative levels of estrogen receptor (ER) (2) . Tumors with different ER subtype differ in other molecular features including histologic grade, proliferation, and genomic alteration pattern, all of which could indicate therapeutic options and predict disease prognosis (3) . ERnegative and ER-positive breast cancers differ in etiology, genetic predisposition, clinical presentation, and disease dynamic. Patients with ER-negative breast cancer tend to be younger, are more likely to carry BRCA1 pathogenic variants, are insensitive to hormonal thera

FAQs

What was the main objective of the study?

To determine whether the risk of estrogen receptor (ER)–specific breast cancer differs according to the ER status of female first-degree relatives’ breast cancers and whether other first-degree relatives’ cancers are also associated with ER subtypes.

How was the study designed and who was included?

A population-based cohort included 464,707 cancer-free women in Stockholm, Sweden, followed between 1978 and 2019, with analyses stratified by ER-positive and ER-negative breast cancer outcomes.

What did the study find about family history of ER-positive or ER-negative breast cancer?

Women with familial ER-positive breast cancer had higher risk of the ER-positive subtype (HR 1.87), and women with familial ER-negative breast cancer had higher risk of ER-negative subtype (HR 2.54), with risk increasing by number of concordant relatives and younger age at diagnosis.

Sep 24, 2026

Uploaded by Cipher