Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women
Rosenberg L,Boggs DA,Wise LA,Adams-Campbell LL,Palmer JR
Published July 22, 2010Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, 19(8), 2073-2079
Rosenberg, L., Boggs, D. A., Wise, L. A., Adams-Campbell, L. L., & Palmer, J. R. (2010). Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 19(8), 2073-2079. https://doi.org/10.1158/1055-9965.EPI-10-0428
Rosenberg L, Boggs DA, Wise LA, Adams-Campbell LL, Palmer JR. Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women. Cancer Epidemiol Biomarkers Prev. 2010;19(8):2073-2079. doi:10.1158/1055-9965.EPI-10-0428
Rosenberg, L., et al. "Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol. 19, no. 8, 2010, pp. 2073-2079.
Georgetown Lombardi Comprehensive Cancer Center035zrb927
Linked to ROR, the Research Organization Registry
Abstract
Background
Oral contraceptive formulations have changed over time, making it relevant to assess the effect of more recent formulations on breast cancer risk. In addition, some studies have found stronger positive associations of oral contraceptive use with estrogen receptor-negative (ER(-)) than with ER-positive (ER(+)) breast cancer. We carried out the first assessment of the effect of oral contraceptive use on the incidence of breast cancer classified by receptor status among African American women, a group disproportionately affected by ER(-) cancer.
Methods
We followed 53,848 Black Women's Health Study participants from 1995 to 2007 through biennial health questionnaires, in which participants reported information about incident breast cancer, oral contraceptive use, and breast cancer risk factors. Pathology information was obtained on receptor status for 789 incident cases. Incidence rate ratios (IRR) with 95% confidence intervals (95% CI) were derived from Cox regression models with control for confounding factors.
Results
Ever use of oral contraceptives was more strongly associated with ER(-)PR(-) breast cancer (279 cases; IRR, 1.65; 95% CI, 1.19-2.30) than with ER(+)PR(+) cancer (386 cases; IRR, 1.11; 95% CI, 0.86-1.42). The risk of ER(-)PR(-) breast cancer increased with increasing duration of use among recent users.
Conclusions
These results indicate that the oral contraceptive formulations used in recent decades increase breast cancer risk in African American women, with a greater effect for ER(-) than ER(+) cancer.
Impact
Mechanisms to explain the adverse influence of oral contraceptive use on ER(-) breast cancer need to be elucidated.
Velmahos AH et al., 2026·Journal of Restorative Reproductive Medicine·Free to read
To evaluate the extent to which a history of infertility is associated with adherence to specific diets among reproductive-aged females. Cross-sectional analysis Between 2017–2023, 7,227 North American female pregnancy planners aged 21-45 years enrolled in PRESTO (Pregnancy Study Online), a preconception cohort study. Participants completed self-administered baseline questionnaires during preconception. Exposure: Infertility history, defined as: 1) self-reported 12-month clinical infertility, 2) history of visiting a clinician for an infertility work-up, and/or 3) clinician-identified cause of infertility (e.g., ovulatory or tubal). Adherence to specific diets, including vegetarian, vegan, Mediterranean, Paleo, Weight Watchers®, ketogenic, dairy free, gluten free, Atkins®, South Beach®, Zone®, raw foods, or other at baseline. Multivariable log-binomial regression models estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs), adjusted for age, income, and body mass index (BMI). The percentage of participants with a history of infertility was 26% based on the 12-month clinical infertility definition, 30% based on visiting a physician for infertility evaluation, and 26% based on an infertility diagnosis following a physician visit. Overall adherence to any particular diet was low (4.6% vegetarian, 2.8% ketogenic, 1.7% Weight Watchers®, 1.4% Mediterranean, 1.3% vegan, 0.8% Paleo, and all other diets: <0.8%); 86.6% reported not adhering to any particular diet. A history of 12-month clinical infertility was associated with lower adherence to vegetarian (PR=0.78; 95% CI: 0.60-1.03), Paleo (PR=0.43; 95% CI: 0.19-0.98), and Weight Watchers® (PR=0.55; 95% CI: 0.34-0.91) diets. An infertility history involving a medical work-up was associated with a higher prevalence of adherence to a ketogenic diet (PR=1.56; 95% CI: 1.17-2.09). Participants whose infertility was attributed to ovulatory or tubal causes were nearly two times more likely to adhere to a ketogenic diet (PR=2.01; 95% CI: 1.38-2.94; PR=2.22; 95% CI: 1.09-4.49, respectively). The cross-sectional design cannot establish temporality or causality. Data on dietary patterns and infertility history were self-reported, which can introduce misclassification. Generalizability may be limited because participants were pregnancy planners not using fertility treatments; participants were also more likely to be non-Hispanic White and of higher socioeconomic status than the general population. The ketogenic diet was more prevalent among females with an infertility history, while vegetarian, Paleo, and Weight Watchers® diets were less prevalent. These associations mirror the results of studies evaluating the reverse relationship, suggesting that some patients with infertility seek information for behavioral modifications via evidence-based medicine.
Pedersen ES et al., 2024·Paediatr Perinat Epidemiol·Free full text on PubMed Central
The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility-promoting tools. To investigate the association between fertility indicators and fecundability in Danish women trying to conceive. Web-based preconception cohort study. We analysed data from 11,328 females aged 18-49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007-2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self-reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities regression models adjusted for age, socio-economic position, health indicators, reproductive history and gynaecological factors. Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non-use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow-up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31). In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator.
Mitro SD et al., 2024·JAMA network open·Free full text on PubMed Central
Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development. To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife. DESIGN, SETTING, The Study of Women's Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024. Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized. Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses. Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk. Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.
Wise LA et al., 2023·Fertil Steril·Free full text on PubMed Central
To assess the effect of randomization to FertilityFriend.com, a mobile computing fertility-tracking app, on fecundability.
Parallel non-blinded randomized controlled trial nested within the Pregnancy Study Online (PRESTO), a North American preconception cohort. PATIENT(S): Female participants aged 21 to 45 years attempting conception for ≤6 menstrual cycles at enrolment (2013-2019). Randomization (1:1) of 5532 participants to receive a premium Fertility Friend (FF) subscription. MAIN OUTCOME MEASURE(S): Fecundability (per-cycle probability of conception). Participants completed bimonthly follow-up questionnaires until pregnancy or a censoring event, whichever came first. We first performed an intent-to-treat analysis of the effect of FF randomization on fecundability. In secondary analyses, we used a per-protocol approach that accounted for adherence in each trial arm. In both analyses, we used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) comparing those randomized vs. not randomized and applied inverse probability weights to account for loss-to-follow-up (intent-to-treat and per-protocol analyses) and adherence (per-protocol analyses only). Using life-table methods, 64% of the 2775 participants randomized to FF and 63% of the 2767 participants not randomized to FF conceived during 12 cycles; these respective percentages were each 70% among those with 0-1 cycles of attempt time at enrolment. Of those randomized to FF, 72% were defined as adherent (68% of observed menstrual cycles). In intent-to-treat analyses, there was no appreciable association overall (FR = 0.97; 95% CI, 0.90-1.04) or within strata of pregnancy attempt time at enrolment, age, education, or other characteristics. In per-protocol analyses, we observed little association overall (FR = 1.06; 95% CI, 0.99-1.14), but weak-to-moderate positive associations among participants who had longer attempt times at enrolment (FR = 1.15; 95% CI, 0.98-1.35 for 3-4 cycles; FR = 1.14; 95% CI, 0.87-1.48 for 5-6 cycles), were aged <25 years (FR = 1.29; 95% CI, 1.01-1.66), had ≤12 years of education (FR = 1.32; 95% CI, 0.92-1.89), or were non-users of hormonal contraception within 3 months before enrolment (FR = 1.10; 95% CI, 1.02-1.19). No appreciable associations were observed in intent-to-treat analyses. In secondary per-protocol analyses that accounted for adherence, randomization to FF was associated with slightly greater fecundability among selected subgroups of participants; however, these results are susceptible to unmeasured confounding.
Bethea TN et al., 2015·Breast Cancer Res·Free full text on PubMed Central
Recent oral contraceptive (OC) use has been consistently associated with increased risk of breast cancer, but evidence on specific breast cancer subtypes is sparse. We investigated recency and duration of OC use in relation to molecular subtypes of breast cancer in a pooled analysis of data from the African American Breast Cancer Epidemiology and Risk Consortium. The study included 1,848 women with estrogen receptor-positive (ER+) breast cancer, 1,043 with ER-negative (ER-) breast cancer (including 494 triple negative (TN) tumors, which do not have receptors for estrogen, progesterone, and human epidermal growth factor 2), and 10,044 controls. Multivariable polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for exposure categories relative to never use, controlling for potential confounding variables. OC use within the previous 5 years was associated with increased risk of ER+ (OR 1.46, 95% CI 1.18 to 1.81), ER- (OR 1.57, 95% CI 1.22 to 1.43), and TN (OR 1.78, 95% CI 1.25 to 2.53) breast cancer. The risk declined after cessation of use but was apparent for ER+ cancer for 15 to 19 years after cessation and for ERbreast cancer for an even longer interval after cessation. Long duration of use was also associated with increased risk of each subtype, particularly ER-. Our results suggest that OC use, particularly recent use of long duration, is associated with an increased risk of ER+, ER-, and TN breast cancer in African American women. Research into mechanisms that explain these findings, especially the association with ERbreast cancer, is needed.
Phipps AI et al., 2011·J Natl Cancer Inst·Free full text on PubMed Central
Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers. Using data from 155,723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk. We used Cox regression to evaluate associations with triple-negative (N = 307) and ER+ (N = 2610) breast cancers and used partial likelihood methods to test for differences in subtype-specific hazard ratios (HRs). Reproductive history was differentially associated with risk of triple-negative and ER+ breast cancers. Nulliparity was associated with decreased risk of triple-negative breast cancer (HR = 0.61, 95% confidence interval [CI] = 0.37 to 0.97) but increased risk of ER+ breast cancer (HR = 1.35, 95% CI = 1.20 to 1.52). Age-adjusted absolute rates of triple-negative breast cancer were 2.71 and 1.54 per 10,000 person-years in parous and nulliparous women, respectively; by comparison, rates of ER+ breast cancer were 21.10 and 28.16 per 10,000 person-years in the same two groups. Among parous women, the number of births was positively associated with risk of triple-negative disease (HR for three births or more vs one birth = 1.46, 95% CI = 0.82 to 2.63) and inversely associated with risk of ER+ disease (HR = 0.88, 95% CI = 0.74 to 1.04). Ages at menarche and menopause were modestly associated with risk of ER+ but not triple-negative breast cancer; breastfeeding and oral contraceptive use were not associated with either subtype. The association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers. These findings require further confirmation because the biological mechanisms underlying these differences are uncertain.
Beaber EF et al., 2014·Cancer Epidemiol Biomarkers Prev·Free full text on PubMed Central
Evidence suggests that recent oral contraceptive (OC) use is associated with a small increased breast cancer risk; yet risks associated with contemporary OC preparations and by molecular subtype are not well characterized. We conducted a population-based case-control study of invasive breast cancer among women ages 20 to 44 residing in the Seattle-Puget Sound area from 2004 to 2010 (985 cases and 882 controls). We collected information on contraceptive use and participant characteristics via an in-person interview. Multivariable-adjusted logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Lifetime duration of OC use for ≥ 15 years was associated with an increased breast cancer risk (OR, 1.5; 95% CI, 1.1-2.2). Current OC use (within 1 year of reference date) for ≥ 5 years was associated with an increased risk (OR, 1.6; 95% CI, 1.1-2.5) and there were no statistically significant differences in risk by OC preparation. Risk magnitudes were generally greater among women ages 20 to 39, and for estrogen receptor-negative (ER(-)) and triple-negative breast cancer (current use for ≥ 5 years among ages 20-39: ER(-) OR, 3.5; 95% CI, 1.3-9.0; triple-negative OR, 3.7; 95% CI, 1.2-11.8), although differences between groups were not statistically significant. Long-term use of contemporary OCs and current use for ≥ 5 years was associated with an increased breast cancer risk among women ages 20 to 44. Risk may be greater among younger women and for ER(-) and triple-negative breast cancer, but these findings require confirmation. Continued surveillance and pooled analyses of OC use and breast cancer risk by molecular subtype are needed as OC preparations evolve.
Rosenberg L et al., 2008·Am J Epidemiol·Free full text on PubMed Central
Oral contraceptive (OC) use has been linked to increased risk of breast cancer, largely on the basis of studies conducted before 1990. In the Case-Control Surveillance Study, a US hospital-based case-control study of medication use and cancer, the authors assessed the relation of OC use to breast cancer risk among 907 case women with incident invasive breast cancer (731 white, 176 black) and 1,711 controls (1,152 white, 559 black) interviewed from 1993 to 2007. They evaluated whether the association differed by ethnicity or tumor hormone receptor status. After control for breast cancer risk factors, the multivariable odds ratio for 1 year or more of OC use, relative to less than 1 year of use, was 1.5 (95% confidence interval: 1.2, 1.8). The estimates were similar within age strata (<50 years and >or= 50 years). The odds ratios were larger for use within the previous 10 years, long-duration use, and black ethnicity, but these differences were not statistically significant. The association of OC use with breast cancer risk did not differ according to the estrogen or progestogen receptor status of the tumor. These results suggest that OC use is associated with an increased risk of breast cancer diagnosed in recent years.
General Gynecology › Breast Health › Breast Cancer Risk · Contraception › Oral Contraceptives › Cancer Risk
Lynn Rosenberg, Lauren A Wise, Julie R Palmer, Deborah A Boggs
L Rosenberg, L Wise, J Palmer, Debbie Boggs, Deb Boggs, D Boggs
PMID 20647407 20647407 DOI 10.1158/1055-9965.EPI-10-0428 10.1158/1055-9965.EPI-10-0428 Rosenberg et al. 2010, Rosenberg 2010
Cite this article
Rosenberg, L., Boggs, D. A., Wise, L. A., Adams-Campbell, L. L., & Palmer, J. R. (2010). Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 19(8), 2073-2079. https://doi.org/10.1158/1055-9965.EPI-10-0428
Rosenberg L, Boggs DA, Wise LA, Adams-Campbell LL, Palmer JR. Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women. Cancer Epidemiol Biomarkers Prev. 2010;19(8):2073-2079. doi:10.1158/1055-9965.EPI-10-0428
Rosenberg, L., et al. "Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol. 19, no. 8, 2010, pp. 2073-2079.
