Journal of the National Cancer Institute, 103(6), 470-477, 2011
Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer
Amanda I Phipps, Rowan T Chlebowski, Ross L. Prentice
Lewis H Kuller, Lucile L. Adams‐Campbell, Dorothy S. Lane, Marcia L Stefanick, Mara Z. Vitolins, Geoffrey C Kabat, Thomas E Rohan, Lucile L Adams-Campbell , Dorothy Lane, Christopher I Li, Anne McTiernan , Jean Wactawski-Wende
Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia
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.
Methods
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).
Results
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.
Conclusion
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.
triple-negative breast cancer oral contraceptive, reproductive history breast cancer subtype, OCP triple-negative breast cancer risk, hormonal factors TNBC, parity breast cancer subtype, oral contraceptive breast cancer receptor status, estrogen receptor negative breast cancer risk, breastfeeding triple-negative protection, contraceptive use cancer subtype, reproductive factors breast cancer molecular
PMID 21346227 21346227 DOI 10.1093/jnci/djr030 10.1093/jnci/djr030
Cite this article
Phipps, A. I., Chlebowski, R. T., Prentice, R., McTiernan, A., Wactawski-Wende, J., Kuller, L. H., Adams-Campbell, L. L., Lane, D., Stefanick, M. L., Vitolins, M., Kabat, G. C., Rohan, T. E., & Li, C. I. (2011). Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer. Journal of the National Cancer Institute, 103(6), 470-477. https://doi.org/10.1093/jnci/djr030
Phipps AI, Chlebowski RT, Prentice R, McTiernan A, Wactawski-Wende J, Kuller LH, et al. Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer. J Natl Cancer Inst. 2011;103(6):470-477. doi:10.1093/jnci/djr030
Phipps, A. I., et al. "Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer." Journal of the National Cancer Institute, vol. 103, no. 6, 2011, pp. 470-477.
Hormone-based contraception disrupts hormonal balance, creating artificial states of anovulation and threatening women's health. We reviewed its main adverse effects and mechanisms on accelerated ovarian aging, mental health (emotional disruptions, depression, and suicide), sexuality (reduced libido), cardiovascular (brain stroke, myocardial infarction, hypertension, and thrombosis), and oncological (breast, cervical, and endometrial cancers). Other "collateral damage" includes negative effects on communication, scientific mistrust, poor physician-patient relationships, increased patient burden, economic drain on the healthcare system, and environmental pollution. Hormone-sensitive tumors present a dilemma owing to preventing some cancers vs. higher risk for others remains controversial, with denial or dismissal as non-relevant adverse effects, information avoidance, and modification of scientific criteria. This lack of clinical assessment poses challenges to women's health and their right to autonomy. Overcoming these challenges requires an anthropological integration of sexuality, as the focus on genital bodily union alone fails to encompass the intimate relational expression of individuals, complete sexual satisfaction, and the intertwined feelings of trust, safety, tenderness, and endorsement of women's femininity.
Contraception/ComparisonReproductive Endocrinology
Open Access
Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression. This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs. We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR = 1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR = 1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR = 1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR = 1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression. Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.
Contraception/ComparisonReproductive Endocrinology
Open Access
The incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurrence of depression in females that begins in early adolescence. In this study, we examine whether and how introducing synthetic estrogen and progestin derivatives through the use of combined hormonal contraceptives (CHC), affects adolescent females' risk for developing depression. We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning. Using a longitudinal cohort design, we will follow a sample of adolescent females over the span of three years. Participants will be once when they are between 13 and 15 years of age, and at approximately 18 and 36 months after their initial assessment. Each time point will consist of two online sessions during which participants will complete a clinical interview that screens for key symptoms of mental health disorders, along with a series of questionnaires assessing their level of depressive symptoms and history of contraceptive use. They will also complete a standardized social-evaluative stress test and an emotion recognition task, as well as provide saliva samples to allow for assessment of their circulating free cortisol levels. In this study we will assess the effect of CHC use during adolescence on development of Major Depressive Disorder (MDD). We will control for variables previously found to or proposed to partially account for the observed relationship between CHC use and MDD, including socioeconomic status, age of sexual debut, and CHC-related variables including age of first use, reasons for use, and its duration. In particular, we will discover whether CHC use increases depressive symptoms and/or MDD, whether elevated depressive symptoms and/or MDD predict a higher likelihood of starting CHC, or both. Furthermore, this study will allow us to clarify whether alterations in stress reactivity and social-emotional functioning serve as pathways through which CHC use may result in increased risk of depressive symptoms and/or MDD.
Contraception/ComparisonReproductive Endocrinology
Open Access
Contraceptive agents are widely used by women of reproductive age, and resulting depression is the most common side effect of this usage. This study aimed to study the effect of monthly injectable combined contraceptives versus that of combined oral contraceptive pills (COC) on patients' mood. A prospective cohort study was conducted on 124 females aged 18-45 years attending the Kom-Ashfeen Family Medicine Unit, El-Kalyubia, Egypt. Participants were divided into three groups group A included 44 participants who received monthly combined injectable contraceptives (CIC); group B included 40 participants who took COC; and group C included 40 participants who used the copper intrauterine device (IUD). The Patient Health Questionnaire-9 (PHQ-9) score was assessed at the beginning of the study and after 6 months of follow-up. After 6 months of follow-up, there were mild but statistically significant increases in the PHQ-9 score in groups A and B, with group A (CIC users) showing the highest increase. Approximately 34.1%, 27.5%, and 15% of CIC, COC, and IUD users, respectively, moved from the non-depression stage to mild depression after 6 months; this change was statistically significant in groups A and B only. Monthly injectable combined contraceptives and oral contraceptive pills were associated with an increased risk of developing mild depression; this risk was higher in users of CICs, although the difference was not statistically significant. Thus, it is crucial to counsel patients about this possible risk and to follow them up. However, further studies are required to confirm our results.