Risk factors for breast cancer subtypes by race and ethnicity: a scoping review

Abstract

Background: Breast cancer consists of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated.

Methods: We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White. We reviewed publications between January 1, 1990 and July 1, 2022. Etiologic heterogeneity evidence (convincing, suggestive, none, or inconclusive) was determined by expert consensus.

Results: Publications per risk factor ranged from 14 (benign breast disease history) to 66 (parity). Publications were most abundant for White women, followed by Asian, Black or African American, and Hispanic or Latina women. Etiologic heterogeneity evidence was strongest for parity, followed by age at first birth, postmenopausal body mass index, oral contraceptive use, and estrogen-only and combined menopausal hormone therapy. Evidence was limited for other risk factors. Findings were consistent across racial and ethnic groups, although the strength of evidence varied.

Conclusion: The literature supports etiologic heterogeneity by ER for some established risk factors that are consistent across race and ethnicity groups. However, in non-White populations evidence is limited. Larger, more comparable data in diverse populations are needed to better characterize breast cancer etiologic heterogeneity.

Figure 1.

Summary of evidence for heterogeneity of associations with risk for breast cancer by estrogen receptor (ER) tumor status^a among diverse racial and ethnic populations. ^aER-positive includes subtypes defined as hormone receptor positive, luminal, luminal A, or ER-positive and PR-positive. ER-negative includes subtypes defined as triple negative or basal-like, and hormone receptor negative or ER-negative and PR-negative. ^bFewer than three published studies for either estrogen receptor positive or negative subtype. BMI = body mass index; MHT = menopausal hormone therapy; PR = progesterone receptor.

Figure 2.

Published estimates for the effect of parity on breast cancer risk by tumor subtype and racial and ethnic group. ^aPooled studies. Estimates for triple negative subtype (ER-, PR-, HER2-) and basal-like subtype are plotted with an open circle. I. Case-control estimates, stratified by tumor subtype, grouped by risk factor definition (A, B, C, D) and colored by racial and ethnic group. II. Case-control estimates pooled within risk factor definition categories (A, B, C, D), stratified by tumor subtype, and colored by racial and ethnic group. III. Case-only estimates comparing risk of ER negative subtype to ER positive, grouped by risk factor definition (A, B, C, D) and colored by racial and ethnic group. A) Per birth, per 1.6 births. B) ≥1 vs 0 births, ≥2 vs (0, <2) births. C) ≥3 vs (0, 1, <3) births, ≥4 vs (0, 1) births. D) ≥5 vs (0, <3) births, ≥6 vs (0, <2) births, ≥7 vs 0 births. ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; PR = progesterone receptor.

Figure 3.

Published estimates for the effect of age at first birth on breast cancer risk by tumor subtype and racial and ethnic group. ^aPooled studies. Estimates for triple negative subtype (ER-, PR-, HER2-) and basal-like subtype are plotted with an open circle. I. Case-control estimates, stratified by tumor subtype, grouped by risk factor definition (A, B, C, D) and colored by racial and ethnic group. II. Case-control estimates pooled within risk factor definition categories (A, B, C, D), stratified by tumor subtype, and colored by racial and ethnic group. III. Case-only estimates comparing risk of ER negative subtype to ER positive, grouped by risk factor definition (A, B, C, D) and colored by racial and ethnic group. A) Per 1 year, per 5 years. B) ≥20 vs <20 years, ≥22 vs <19 years, >24.3 vs ≤24.3, ≥25 vs (<19, 20, 21, 25) years, ≥26 vs <(19, 23, 25, 26) years, ≥28 vs <(23, 24) years, ≥29 vs <25 years. C) Nulliparous or ≥30 vs <20 years, ≥30 vs Nulliparous, ≥30 vs <(18, 19, 20, 21, 24, 25, 30) years. D) ≥31 vs <(21, 23, 31) years, ≥32 vs <22 years, ≥35 vs <(20, 21) years. ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; PR = progesterone receptor.

Figure 4.

Published estimates for the effect of premenopausal BMI on breast cancer risk by tumor subtype and racial and ethnic group. ^aPooled studies. Estimates for triple negative subtype (ER-, PR-, HER2-) and basal-like subtype are plotted with an open circle. I. Case-control estimates, stratified by tumor subtype, grouped by risk factor definition (A, B, C) and colored by racial and ethnic group. II. Case-control estimates pooled within risk factor definition categories (A, B, C), stratified by tumor subtype, and colored by racial and ethnic group. III. Case-only estimates comparing risk of ER negative subtype to ER positive, grouped by risk factor definition (A, B, C) and colored by racial and ethnic group. A) Per 1 unit, per 5 units, per standard deviation, per WHO BMI category. B) ≥25 vs <25, >25.1 vs ≤21.4, >27 vs ≤25, ≥28 vs. ≤24, >28 vs <23, ≥28.3 vs <22.2. C) ≥30 vs <(18.5, 20, 22.5, 25, 30), ≥30.7 vs ≤22.89, ≥35 vs <(18.5, 25). ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; PR = progesterone receptor.

Figure 5.

Published estimates for the effect of postmenopausal BMI on breast cancer risk by tumor subtype and racial and ethnic group. ^aPooled studies. Estimates for triple negative subtype (ER-, PR-, HER2-) and basal-like subtype are plotted with an open circle. I. Case-control estimates, stratified by tumor subtype, grouped by risk factor definition (A, B, C) and colored by racial and ethnic group. II. Case-control estimates pooled within risk factor definition categories (A, B, C), stratified by tumor subtype, and colored by racial and ethnic group. III. Case-only estimates comparing risk of ER negative subtype to ER positive, grouped by risk factor definition (A, B, C) and colored by racial and ethnic group. A) Per 1 unit, per 5 units, per standard deviation, per WHO BMI category. B) >24 vs ≤24, ≥25 vs <25, >25.1 vs ≤21.4, >27 vs. ≤25, ≥28 vs ≤24, >28 vs <23, ≥28.3 vs <22.2. C) ≥30 vs <(18.5, 20, 22.5, 25, 30), ≥30.7 vs ≤22.89, ≥35 vs <(18.5, 25). ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; PR = progesterone receptor.