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  1. 1

    Birth control and breast cancer: An unclear connection.

    Nelson B

    Cancer Cytopathology. 2018 Sep; 126(9):751-752.

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  2. 2
    Peer Reviewed

    Estimating child mortality associated with maternal mortality from breast and cervical cancer.

    Mailhot Vega RB; Balogun OD; Ishaq OF; Bray F; Ginsburg O; Formenti SC

    Cancer. 2018 Nov 1;

    BACKGROUND: Large-scale population studies demonstrate an association between mothers' deaths and child mortality in both lower and higher income countries. The authors estimated children's deaths in association with mothers' deaths from breast or cervical cancer, 2 common cancers in low-income and middle-income countries affecting women of reproductive age, to develop a comprehensive assessment of the death burden of these cancers. METHODS: A Monte Carlo simulation model was devised whereby women were at risk of dying from breast cancer, cervical cancer, or another cause. Compared with children who have living mothers, children of women who die before they reached age 10 years have an elevated risk of death from all causes. Therefore, simulations were conducted, and the impact of mothers' deaths from cervical and breast cancer on associated child mortality was quantified for Bangladesh, Burkina Faso, and Denmark (benchmark analysis), then the analyses were extended to all African countries. RESULTS: Benchmark estimates of child deaths associated with mothers' deaths from breast and cervical cancer resulted in an increment in cancer-related mortality of approximately 2% in Bangladesh, 14% in Burkina Faso, and less than 1% in Denmark. The model predicted an increment in comprehensive cancer deaths when including child death estimates by as high as 30% in certain African countries. CONCLUSIONS: To the authors' knowledge, this is the first study to estimate the impact of a mother's death from cancer on child mortality. The model's estimates call for further investigation into this correlation and underscore the relevance of adequate access to prevention and treatment among women of childbearing age. (c) 2018 American Cancer Society.
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  3. 3
    Peer Reviewed

    Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy.

    Brinton LA; Brogan DR; Coates RJ; Swanson CA; Potischman N; Stanford JL

    Menopause. 2018 Nov; 25(11):1195-1200.

    OBJECTIVE: To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure. DESIGN: A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted. RESULTS: Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0). When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation. CONCLUSIONS: Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy.
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  4. 4
    Peer Reviewed

    Suboptimal Use of Effective Contraceptive Methods in Young Mexican Women With Breast Cancer.

    Castro-Sanchez A; Martinez-Cannon BA; Platas A; Mohar A; Fonseca A; Vega Y; Fimbres-Morales A; Villarreal-Garza C

    Journal of Global Oncology. 2018 Oct; (4):1-7.

    PURPOSE: Contraceptive counseling and adherence in young women with breast cancer (BC) is a relevant issue because chemotherapy and hormonal treatment resulting in amenorrhea do not preclude unintended pregnancies. Currently, there is limited evidence from high-income countries; however, there are no studies regarding use of contraceptives in patients with BC in Mexico. This study aimed to determine the rate of contraceptive use in young Mexican women with BC during cancer treatment, characterize their contraceptive preferences, and assess contraceptive counseling by Mexican physicians. PATIENTS AND METHODS: A cross-sectional survey was conducted regarding contraceptive use and counseling among women age 40 years or younger at BC diagnosis who had completed chemotherapy in the previous 5 years or who were currently receiving long-term treatment with hormonal therapy and/or trastuzumab at a large tertiary health care facility in Mexico. RESULTS: Of a total of 104 eligible women with median age at diagnosis of 34 years, 51.1% reported using a contraceptive during chemotherapy and 45.7% reported using a contraceptive during other types of cancer treatment (hormonal therapy and trastuzumab). Of the 51 patients (49%) who were sexually active during chemotherapy, 76.5% used contraception, but only 29.4% used an effective contraceptive method. When asked about contraceptive counseling, only 16.7% recalled being advised by their health care provider. Sexually active women who received contraceptive counseling used contraceptives more often than women who were not counseled (83.3% v 22.2%). CONCLUSION: A minority of young women with BC in Mexico use effective contraception methods during cancer treatment and receive contraceptive counseling. Informing all premenopausal patients with BC about effective use of contraception methods during treatment should be an essential aspect of the supportive care of young women.
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  5. 5

    Hormonal Contraception and Breast Cancer Risk.

    White ND

    American Journal of Lifestyle Medicine. 2018 May-Jun; 12(3):224-226.

    Contemporary hormonal contraception formulations contain lower doses of estrogen, have new synthetic progestin components, and provide novel methods of delivery that have not been studied extensively in relation to breast cancer risk. Given that hormonal contraception is the leading method of birth control in the United States, it is important to reevaluate risk using current formulations. Recent studies including contemporary hormonal contraception formulations will be described.
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  6. 6
    Peer Reviewed

    Health outcomes associated with use of hormonal contraception: breast cancer.

    Schneyer R; Lerma K

    Current Opinion In Obstetrics and Gynecology. 2018 Dec; 30(6):414-418.

    PURPOSE OF REVIEW: To review recent literature on health outcomes associated with use of hormonal contraception with a focus on breast cancer. RECENT FINDINGS: A large cohort study documented an increased risk of breast cancer among hormonal contraceptive users compared to those who had never used hormonal contraception. The overall relative risk of breast cancer among current or recent users was 1.2 [95% confidence interval (CI), 1.14-1.26]. Overall, this translates into one additional case of breast cancer for every 7690 users of hormonal contraception. Recent publications have also documented a decrease in risk for endometrial, ovarian, and colorectal cancers among hormonal contraceptive users. Based on these data, it is estimated that a third of endometrial and ovarian cancers and a fifth of colorectal cancers were prevented with combined oral contraceptive use. SUMMARY: Several factors must be taken into consideration regarding the risk of breast cancer associated with hormonal contraceptive use. Contraceptive benefits related to preventing unintended pregnancy are protective against associated maternal morbidity and mortality. Noncontraceptive benefits of protecting against other types of cancers must also be considered. Overall, breast cancer risk is low among hormonal contraceptive users and women should be counseled accordingly.
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  7. 7
    Peer Reviewed

    Oral Contraceptive Progestin and Estrogen Use and Increases in Breast, Ovarian, and Endometrial Cancers.

    Grant EC

    JAMA Oncology. 2018 Nov 1; 4(11):1623.

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  8. 8
    Peer Reviewed

    Oral Contraceptive Progestin and Estrogen Use and Increases in Breast, Ovarian, and Endometrial Cancers-Reply.

    Michels KA; Trabert B

    JAMA Oncology. 2018 Nov 1; 4(11):1623-1624.

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  9. 9
    Peer Reviewed

    Hormonal contraception and breast cancer.

    Westhoff CL; Pike MC

    American Journal of Obstetrics and Gynecology. 2018 Aug; 219(2):169.e1-169.e4.

    The recent Danish cohort study reported a 20% increased risk of breast cancer among current and recent hormonal contraception users. These results are largely consistent with previous studies. This study did not report on stage of disease at diagnosis and it is not clear to what extent the apparent increased risk may be due to a small advance in the timing of diagnosis. This study did not report on the risk associated with the use of a 20-mug ethinyl estradiol pill. They did find an increasing risk in current users of longer duration and an increased risk with use of the levonorgestrel intrauterine system-both of these potentially important findings have not been consistently found in previous studies and require further investigation. The breast cancer effects described now in multiple studies wane with time, and in the long-term hormonal contraception use has been found not to be associated with any increased total cancer risk. Copyright (c) 2018 Elsevier Inc. All rights reserved.
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  10. 10

    The Impact of Hormonal Contraceptives on Breast Cancer Pathology.

    Dorchak JA; Maria S; Guarinoni JL; Duensing A; Somiari S; Cavanaugh J; Deyarmin B; Hu H; Iida J; Shriver CD; Witt-Enderby PA

    Hormones and Cancer. 2018 Aug; 9(4):240-253.

    This retrospective case series study, using data obtained through questionnaires and histopathological diagnoses from 656 patients enrolled in the Department of Defense (DoD) Clinical Breast Care Project (CBCP), evaluated associations between hormonal contraceptive use and breast cancer pathology including benign breast pathologies. Three combination hormonal contraceptive agents (COCs) Lo Ovral (LO), Ortho Novum (ON), and Ortho Tri-Cyclen (OTC) were evaluated as they represented the most commonly used hormonal contraceptives in our cohort. The results of this study suggest that the ever use of LO + ON + OTC does not influence the overall incidence of benign breast condition or malignant disease compared to other COCs; however, patients that have used OTC had an association with a diagnosis of benign or luminal A pathologies whereas ON was associated with a diagnosis of benign and DCIS; LO showed no association with any diagnosis-benign or malignant. Patients that have used LO or ON were more likely to be diagnosed with breast cancer at age >/= 40 years whereas patients that had ever used OTC were likely to be diagnosed before the age of 40. Caucasians were less likely to have used OTC and more likely to have used ON; however, use of either hormonal agent positively correlated with premenopausal status at diagnosis and having a benign condition. Age at diagnosis, ethnicity, BMI, family history, menstruation status, and duration of use were all independent predictors of different histopathological subtypes. We conclude that patient-specific variables should be considered when deciding on which type of hormonal contraceptive to use to minimize the risk of developing breast cancer or a breast-related pathology.
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  11. 11
    Peer Reviewed

    Hormonal contraceptives and breast cancer: Clinical data.

    Zolfaroli I; Tarin JJ; Cano A

    European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2018 Nov; 230:212-216.

    The endocrine background of breast cancer has raised questions about the increase in risk that might bear the use of hormonal contraceptives. This has been a particular issue in the case of young women, who constitute the population of contraceptive consumers. Observational studies have been the main source of evidence, which has mainly limited to the combined estrogen-progestogen preparations, the popular pill. Studies in the 80's and 90's of the past century found a small, around a 20%, increase in risk. The translation in absolute number of excess cases has been exiguous because the prevalence of the disease is relatively small in premenopausal women. Moreover, the risk slowly seemed to disappear after 5-10years of use. The more sophisticated analyses provided by new technologies, together with the powerful central registries in some countries, has confirmed increased risk of similar size. Recent preparations, with lower doses of estrogens and new progestogenic molecules, have not substantially modified the risk size. The impact of progestogen only alternatives, either pills or progestogen-loaded intrauterine devices, seems to be similar, but the evidence is still insufficient. Whether there is a preferential effect on histological or molecular subtypes of breast tumours is being debated yet. The data on women at higher risk, either with mutations of the BRCA1/2 genes or with familial weight, have not found specific response patterns, but the experience is still meagre. It is of interest that long-term follow up data on women who enrolled in the initial cohorts, like that of the Royal College of General Practitioners', have shown a considerable protection against cancer of the ovary (relative risk, RR 0.67), endometrium (RR 0.66), or colorectum (RR 0.81). Copyright (c) 2018 Elsevier B.V. All rights reserved.
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  12. 12
    Peer Reviewed

    Hormonal Contraceptive Use Among Women of Older Reproductive Age: Considering Risks and Benefits.

    Tepper NK; Godfrey EM; Folger SG; Whiteman MK; Marchbanks PA; Curtis KM

    Journal of Women's Health. 2018 Apr; 27(4):413-417.

    As women approach menopause, fertility declines but pregnancy can still occur. Maternal and infant risks are increased among women of older reproductive age compared with younger women. A high proportion of pregnancies among women of older reproductive age are unintended and these pregnancies can also be associated with negative maternal and infant consequences. However, women and their healthcare providers may have concerns about risks associated with contraceptive use, particularly combined hormonal contraceptives, among women of older reproductive age who already may be at increased risk for conditions such as cardiovascular disease and breast cancer. Nonetheless, available evidence does not suggest that hormonal contraceptive use among women of older reproductive age substantially increases age-related risks of cardiovascular events or breast cancer. CDC recommends that contraception is still needed for women older than 44 years who have not reached menopause and wish to avoid pregnancy, and that based on age alone, all contraceptive methods are considered safe or generally safe for use by women of older reproductive age.
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  13. 13

    Breast cancer and hormonal contraception: Should we rethink our concepts?

    Borges JBR; Torresan RZ

    Revista Da Associacao Medica Brasileira. 2018 Mar; 64(3):201-203.

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  14. 14

    Contemporary Hormonal Contraception and the Risk of Breast Cancer [letter]

    Schwarz EB; Foster DG; Grossman D

    New England Journal of Medicine. 2018 Mar 29; 378(13):1263-4.

    Mørch et al. (Dec. 7 issue) have reignited concerns about the safety of a range of contemporary hormonal contraceptive methods. Since a diagnosis of cancer is frequently interpreted as a death sentence, it is unfortunate that the authors did not report their findings on the effects of hormonal contraceptives on either the rate of death from breast cancer or the rate of death from any cause. This is a particular concern because multiple high-quality studies have shown that the use of hormonal contraceptives is associated with a significantly lower risk of death from any cause than the risk associated with never having used these contraceptive methods. Given the ongoing global epidemic of maternal deaths, clinicians and policymakers must remember that even in developed countries, childbirth remains a risk to women’s health. Thus, lack of consideration of all-cause mortality when discussing contraceptive safety has grave implications. Women who receive prescription medications (such as hormonal contraceptives) are generally more likely to receive clinical screening and an early diagnosis of cancer than those who do not receive prescription medications. When screening results in early diagnosis and treatment, reducing the rate of cancer-related deaths and all-cause mortality, we consider it a public health success. The same standards must be applied when discussing contraceptive safety. (full text)
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  15. 15

    Contemporary Hormonal Contraception and the Risk of Breast Cancer [letter]

    Wood S

    New England Journal of Medicine. 2018 Mar 29; 378(13):1264.

    The findings reported by Mørch et al. of an increase in the risk of breast cancer associated with contemporary hormonal contraceptives are certainly disappointing. I was particularly surprised to see an increase in risk with the levonorgestrel-releasing intrauterine system. Can the authors share any data on nonhormonal contraceptive choices — specifically the copper intrauterine device (IUD)? If there was no apparent increase in risk with the use of this product, then readers might be more confident that residual confounding was not the source of the association with breast cancer. (full text)
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  16. 16

    Contemporary Hormonal Contraception and the Risk of Breast Cancer [letter]

    Roberts K; Merkatz RB; Vieira CS

    New England Journal of Medicine. 2018 Mar 29; 378(13):1264.

    The data in Table 3 of the article by Mørch et al. (available at suggest that even after discontinuation of hormonal contraception, the risk of breast cancer was still higher among women who used hormonal contraceptives for 5 years or more than among those who had never used them. Statistically, the valid way to make such an inference is first to present a global P value of an interaction between the duration of contraceptive use and time since last use; this information was not provided. If the global P value indicates significance, then additional inferences can be made with an adjustment for multiplicity.1 Without these approaches, authors may erroneously reject a null hypothesis of no interaction, and the type I error rate from the pairwise comparisons may be inflated and lead to spurious claims of statistical significance. Although adjustment for multiplicity in epidemiologic studies remains controversial,1-3 when the effect size is small, as indicated by the relative risks presented in Table 3, this approach assumes special importance to avert false positive results and unjustified panic among women who use hormonal contraceptives. (full text)
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  17. 17

    Contemporary Hormonal Contraception and the Risk of Breast Cancer [letter]

    Cramer DW; Braaten K

    New England Journal of Medicine. 2018 Mar 29; 378(13):1264-5.

    Mørch et al. use data from nationwide registries in Denmark to examine contemporary hormonal contraception and the risk of breast cancer. A potential confounder was the age of the women at first birth, since the risk of breast cancer is lower among women who give birth for the first time at an early age than among older women who do, and a woman’s age at first birth is delayed by contraception. Data on age at first birth were abstracted from the Danish National Birth Register, which started in 1973. These data may be missing for older cohort members. Data should be complete for women younger than 35 years of age, so Table S7 in the Supplementary Appendix of the article is important. However, the authors’ analysis was not adjusted for the women’s age at first birth. An important omission was a discussion of how many women underwent tubal sterilization and whether they were placed disproportionately into the “never used hormonal contraception” category. Information about sterilization is available from the Danish National Health Register; this information is complete from 1977 on. This information again may be incomplete for older cohort members. Evidence that sterilization may lower the risk of breast cancer makes this an important issue. Women may choose to delay childbearing even knowing that it will increase their risk of breast cancer. They should not conclude from this study that this risk can be avoided by choosing “nonhormonal” contraceptive methods of an unspecified type and efficacy. (full text)
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  18. 18

    Short-term cancer risks associated with oral contraceptives are balanced by longer term benefits.

    Webb PM; Jordan SJ

    BMJ Evidence - Based Medicine. 2018 Jun; 23(3):115-116.

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  19. 19
    Peer Reviewed

    Contemporary Hormonal Contraception and the Risk of Breast Cancer.

    Nachtigall L; Naftolin F; Keefe DL

    New England Journal of Medicine. 2018 Mar 29; 378(13):1265.

    The article on hormonal contraception and the risk of breast cancer in Denmark is informative. However, it begins with an out-of-date statement regarding the role of estrogen in breast cancer and concludes without mentioning that this study did not show that estrogen has a role in breast cancer; both errors require clarification. Mørch et al. attribute the statement “Estrogen promotes the development of breast cancer” to a 2007 review article that quotes articles from 1979–1988 and discusses possible mechanisms by which progestins trigger the induction of breast cancer by estrogen. These possibilities have not been proved in actual women, and the action of estrogen on breast cancer cells may differ from that on normal breast cells. In the Women’s Health Initiative trial, which involved 27,300 women, there were 15% fewer cases of invasive breast cancer among women in the estrogen-only group than among those in the placebo group. At the 18-year follow-up, the rate of death from breast cancer among women in the estrogen-only group was 45% lower than the rate among women in the placebo group, and the rate of death from breast cancer was 20% higher among women who received estrogen plus synthetic progestin than among women who received placebo. It appears that the administration of progestin, even in progestin-only contraceptives, may increase the risk of breast cancer. The article by Mørch et al. does not show that estrogen, per se, is a breast cancer–causing factor in hormonal contraception. (full text)
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  20. 20
    Peer Reviewed

    Hormonal contraception and risk of breast cancer: a closer look.

    Kaunitz AM; Pinkerton JV; Manson JE

    Menopause. 2018 May; 25(5):477-479.

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  21. 21
    Peer Reviewed

    Weighing the Risks and Benefits of Hormonal Contraception.

    Peachman RR

    JAMA. 2018 Mar 20; 319(11):1083-1084.

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  22. 22
    Peer Reviewed

    Hormonal Contraceptives Increase Breast Cancer Risk.

    Rosenberg K

    American Journal of Nursing. 2018 Mar; 118(3):69.

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  23. 23
    Peer Reviewed

    Progestin-only and combined oral contraceptives and receptor-defined premenopausal breast cancer risk: The Norwegian Women and Cancer Study.

    Busund M; Bugge NS; Braaten T; Waaseth M; Rylander C; Lund E

    International Journal of Cancer. 2018 Jun 1; 142(11):2293-2302.

    Receptor-defined subtypes of breast cancer represent distinct cancer types and have differences in risk factors. Whether the two main hormonal forms of oral contraceptives (OCs); i.e. progestin-only (POC) and combined oral contraceptives (COC), are differentially associated with these subtypes are not well known. The aim of our study was to assess the effect of POC and COC use on hormone receptor-defined breast cancer risk in premenopausal women in a prospective population-based cohort - The Norwegian Women and Cancer Study (NOWAC). Information on OC use was collected from 74,862 premenopausal women at baseline. Updated information was applied when follow-up information became available. Multiple imputation was performed to handle missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for breast cancer. 1,245 incident invasive breast cancer cases occurred. POC use >/=5 years was associated with ER+ (HR = 1.59, 95% CI 1.09- 2.32, ptrend = 0.03) and ER+/PR+ cancer (HR = 1.63, 95% CI 1.07-2.48, ptrend = 0.05), and was not associated with ER- (pheterogeneity = 0.36) or ER-/PR- (pheterogeneity = 0.49) cancer. COC use was associated with ER- and ER-/PR- cancer, but did not increase risk of ER+ and ER+/PR+ cancer. Current COC use gave different estimates for ER/PR-defined subtypes (pheterogeneity = 0.04). This is the first study to show significant associations between POC use and hormone receptor-positive breast cancer. The lack of power to distinguish effects of POC use on subtype development calls for the need of larger studies to confirm our finding. (c) 2018 UICC.
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  24. 24
    Peer Reviewed

    Oral Contraceptives and the Small Increased Risk of Breast Cancer.

    Hunter DJ

    New England Journal of Medicine. 2017 Dec 7; 377(23):2276-2277.

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  25. 25
    Peer Reviewed

    Contemporary Hormonal Contraception and the Risk of Breast Cancer.

    Morch LS; Skovlund CW; Hannaford PC; Iversen L; Fielding S; Lidegaard O

    New England Journal of Medicine. 2017 Dec 7; 377(23):2228-2239.

    BACKGROUND: Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer. METHODS: We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders. RESULTS: Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. CONCLUSIONS: The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).
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