Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.     

Cyclin D1 in Breast Cancer

Cyclin D1 protein plays an important part in regulating the progress of the cell during the G1 phase of the cell cycle. The cyclin D1 gene, CCND1, is amplified in approximately 20% of mammary carcinomas, and the protein is over- expressed in approximately 50% of cases. This has led to intensive study to ascertain whether cyclin D1 is a biological marker in breast cancer; however, the clinical work has produced unexpected results. Work in cell lines and in transgenic mice indicate that CCND1 is a weak oncogene and it was expected that, like c- erbB-2, over-expression of cyclin D1 protein would be associated with a poor prognosis. Early immunohistochemical prognostic studies produced equivocal results but we, and others, have recently shown that strong staining for cyclin D1 is more likely to be seen in well differentiated, estrogen receptor positive carcinomas. Furthermore, we have found that over-expression of cyclin D1 is actually associated with a good outcome, both in terms of prognosis and response to endocrine treatment. Cyclin D1 is frequently over- expressed in ductal carcinoma in situ but not in benign breast disease, including atypical ductal hyperplasia; hence its expression appears to be closely linked with carcinogenesis. In order to help explain the apparent beneficial effects of cyclin D1 over- expression, a number of closely associated cell cycle proteins have also been evaluated, including the cyclin dependent kinase inhibitor p27, which blocks the activating effects of cyclin D1. Initial reports show that high levels of p27 are associated with a good prognosis and we have shown a positive association between p27 and cyclin D1 expression. These clinical results of cyclin D1 are an example of how information obtained from basic cell biology studies needs to be complemented by clinical studies to ascertain the true worth of a prognostic marker.     

Postmenopausal hormone therapy and breast cancer risk: the Multiethnic Cohort

Epidemiological studies indicate that menopausal estrogen-progestin therapy (EPT) use is associated with an increase in breast cancer risk. Further data are needed on whether this association varies by specific prognostic factors and ethnicity. We conducted a cohort study among 55,371 African-American, Native Hawaiian, Japanese-American, Latina and White postmenopausal women aged 45-75 years old in the Multiethnic Cohort Study (MEC). A total of 1,615 incident invasive breast cancer cases were identified over an average of 7.3 years. Adjusted relative risks (RRs) were computed for the various forms of hormone therapy (HT). Assuming current users continued HT use to the end of follow-up, current EPT use was associated with a 29% increased risk of breast cancer per 5 years of use (95% confidence interval (CI) = 23-35%), and current estrogen therapy (ET) use with a 10% increase in risk per 5 years of use (95% CI = 5-16%). These figures increased to only a very small extent when we adjusted for the estimated 3% of such women who stop HT use per year of follow-up. EPT and ET use were associated with greater risk among leaner women, but the increase in risk with EPT use was still very evident in women with BMI > or =30 kg/m(2). Current EPT use was associated with increased risk for ER+/PR+, ER+/PR- and ER-/PR- tumors. There was little difference in risk by stage of disease or histologic subtype. The increase with EPT use was clearly seen in all 5 ethnic groups; and the increase with ET in 4 of the 5 groups.     

激素替代治疗与女性肺癌关系的研究现况分析

肺癌是全球最常见的恶性肿瘤之一,在肿瘤致死原因中居第一位。女性激素替代治疗应用于卵巢功能衰退者以预防疾病、缓解症状。通过了解激素替代治疗应用现况及其与女性肺癌发生风险的研究发现,激素替代治疗可能增加、不增加甚至降低肺癌发生风险。近年来随着个体化给予低剂量的雌和(或)孕激素及新型激素的应用,使激素替代治疗更倾向于不增加肺癌发生风险。目前认为激素替代治疗不构成女性肺癌风险,在适宜人群中应用安全性高的激素,使适龄妇女在低风险的情况下获得最大收益。     

Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow-up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16-3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96-3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74-10.51) compared to the never use of HRT. In current users of combined HRT with testosterone-like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56-6.75, and RR = 1.94, 95% CI = 1.26-3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin.     

Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort

Most epidemiological studies have shown an increase in breast cancer risk related to hormone replacement therapy (HRT) use. A recent large cohort study showed effects of similar magnitude for different types of progestogens and for different routes of administration of estrogens evaluated. Further investigation of these issues is of importance. We assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women who had never taken any HRT 1 year before entering the E3N-EPIC cohort study (mean age at inclusion: 52.8 years); 948 primary invasive breast cancers were diagnosed during follow-up (mean duration: 5.8 years). Data were analyzed using multivariate Cox proportional hazards models. In this cohort where the mean duration of HRT use was 2.8 years, an increased risk in HRT users compared to nonusers was found (relative risk (RR) 1.2 [95% confidence interval 1.1-1.4]). The RR was 1.1 [0.8-1.6] for estrogens used alone and 1.3 [1.1-1.5] when used in combination with oral progestogens. The risk was significantly greater (p <0.001) with HRT containing synthetic progestins than with HRT containing micronized progesterone, the RRs being 1.4 [1.2-1.7] and 0.9 [0.7-1.2], respectively. When combined with synthetic progestins, both oral and transdermal/percutaneous estrogens use were associated with a significantly increased risk; for transdermal/percutaneous estrogens, this was the case even when exposure was less than 2 years. Our results suggest that, when combined with synthetic progestins, even short-term use of estrogens may increase breast cancer risk. Micronized progesterone may be preferred to synthetic progestins in short-term HRT. This finding needs further investigation.     

Human papillomavirus positivity predicts favourable outcome for squamous carcinoma of the tonsil

Mutations in the p53 and retinoblastoma (pRb) pathways associated with the use of tobacco and alcohol are common in squamous cell carcinoma (SCC) of the head and neck. Cell cycle proteins are also affected by human papillomavirus (HPV), which may also have an aetiological role in cancers at particular sites, most notably the tonsil. Attempts to identify prognostic molecular markers in head and neck cancers have met with conflicting results, but few studies have been undertaken with tumours of known HPV status at a single anatomic site. In our study 86 tonsil cancers were analysed for HPV status by sequence analysis of polymerase chain reaction products and for the expression of cell cycle proteins (p53, p21(CIP1/WAF1), pRb, p16(INK4A), cyclin D1 and p27(KIP1)) by immunohistochemistry. The HPV status could be established in 67 of the tumours. Thirty-one (46%) of these were HPV-positive, predominantly (28/31) for HPV16. Findings were related to tumour recurrence and patient survival. None of the cell cycle proteins independently predicted recurrence or survival. Patients with HPV-positive tumours, however, were significantly less likely (p < 0.05) to have recurrence or to die of disease than those with HPV-negative tumours, after adjusting for the effects of the cell cycle proteins, clinical stage, pathological node status, tumour grade, age, gender and treatment. These findings support the concept that HPV-positive tonsil cancers may be a distinct biological group with less aggressive characteristics. Screening of tonsil cancers for HPV DNA may help optimise treatment and provide more accurate prognostic information.     

宫颈恶性肿瘤治疗后激素替代疗法(HRT)对预后的影响

目的：观察宫颈恶性肿瘤治疗后的激素替代疗法（HRT）对预后的影响。方法：对166例宫颈癌治疗后的妇女给予HRT，通过病人主观症状的变化了解替代效果；通过阴道宫颈涂片、B超、胸片、ECT等检查了解病情变化，总结其疗效及对预后的影响。结果：研究组复发转移占12．05％（20／166），对照组中复发转移占15％（24／160），两组无明显差异。肿瘤的复发与病理类型、临床分期有密切关系，与是否采用HRT关系不大。结论：HRT对宫颈鳞癌与腺癌患者都是安全有效的。     

Increased incidence of small and well-differentiated breast tumours in post-menopausal women following hormone-replacement therapy

Exposure to hormone-replacement therapy (HRT) has consistently been associated with an increased incidence of breast cancer, particularly of small tumours. Other tumour characteristics in relation to HRT have received less scientific attention. Our aim in this population-based prospective cohort study was to assess whether HRT is associated with an increased incidence of breast-cancer subgroups defined in terms of stage, type (according to the WHO system), Nottingham grade and the Nottingham Prognostic Index (NPI). Evaluation was based on a cohort of 5,865 post-menopausal women followed for an average of 9.8 years. Twenty percent of women reported current use of HRT at the time of the baseline interview. Record linkage with the Swedish Cancer Registry and local clinical registries identified 141 incident invasive breast-cancer cases. All tumours were reclassified by 1 pathologist. The incidence of breast cancer in HRT users was 377/10(5) and in non-users 221/10(5) person-years [relative risk (RR) = 1.72, 95% confidence interval (CI) 1.17-2.52]. This risk remained statistically significant after adjustment for established risk factors in a Cox proportional hazards analysis (RR = 1.66, 95% CI 1.12-2.45). Among HRT users, there was over-representation of cases with stage I tumours (adjusted RR = 2.33, 95% CI 1.44-3.76), of lobular carcinomas (RR = 4.38, 95% CI 1.60-12.0) and of tubular tumours (RR = 4.81, 95% CI 1.37-16.8). Nottingham grade I/II carcinomas (RR = 2.02, 95% CI 1.29-3.16) and cases with NPI < or = 3.4 (RR = 2.29, 95% CI 1.41-3.72) were similarly over-represented among HRT users. Incidence of breast cancer was increased in post-menopausal women who used HRT at baseline. Among HRT users, there was over-representation of tumours that, with regard to stage, type and grade, are associated with a favourable prognosis.     

Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome.

Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27(Kip1), p21(Waf1) and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (> or =25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21(Waf1) (p = 0.015) and high p27(Kip1) (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (> or =10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease-free survival on a multivariate analysis that also included p27(Kip1) expression and tumor stage. The simultaneous presence of low cyclin D1, low p27(Kip1) and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.     

Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women

Objective To assess postmenopausal breast cancer risk in relation to particular patterns of oral contraceptive (OC) use according to hormone replacement therapy (HRT) exposure.Methods Time-dependent Cox regression models were used to analyse information on postmenopausal women from a large-scale French cohort. Among a total of 68,670 women born between 1925 and 1950, 1405 primary invasive postmenopausal breast cancer cases were identified from 1992 to 2000.Results A non-significant decrease in risk of around 10% was associated with ever OC use as compared to never OC use in postmenopausal women. No significant interaction was found between OC and HRT use on postmenopausal breast cancer risk. Breast cancer risk decreased significantly with increasing time since first OC use (test for trend: p=0.01); this was consistent after adjustment for duration of use or for time since last use.Conclusion No increase in breast cancer risk was associated with previous OC exposure among postmenopausal women, probably because the induction window had closed. Some women may develop breast cancer soon after exposure to OCs, leading to a deficit of cases of older women. Further investigation is therefore required to identify young women at high risk.* Address correspondence to: F. Clavel-Chapelon, Equipe E3N-EPIC, INSERM “Nutrition, Hormones, Cancer”, Institut Gustave-Roussy, 94805 – Villejuif, France.     

The role of menopausal hormone therapy in women with or at risk of ovarian and breast cancers: Misconceptions and current directions

For women who are candidates for menopausal hormone therapy (MHT), estrogen can provide relief from symptomatic menopause, decrease rates of chronic illnesses, and improve health-related quality of life. However, confusion surrounds the evidence regarding the impact of exogenous estrogen and progesterone on the breast and ovary. Available data regarding the risks of MHT (estrogen and/or progestin) related to the development of breast and ovarian cancer are often inconsistent or incomplete. Modern molecular and genetic techniques have improved our understanding of the heterogeneity of breast and ovarian cancer. This enhanced understanding of the disease has impacted our understanding of carcinogenesis. Treatment options have evolved to be more targeted toward hormonal therapy for certain subtypes of disease, whereas cytotoxic chemotherapy remains the standard for other histological and molecular subtypes. The role of MHT in the breast and ovarian cancer survivor, as well as women who are at high risk for the development of hereditary breast and ovarian cancer, remains controversial despite evidence that this treatment can improve quality of life and survival outcomes. Through this article, we examine the evidence for and against the use of MHT with a focus on women who have or are at high risk for breast and ovarian cancer.     

Breast conserving therapy and mastectomy revisited: Breast cancer‐specific survival and the influence of prognostic factors in 129,692 patients

This large population‐based study compared breast‐conserving surgery with radiation therapy (BCT) with mastectomy on (long‐term) breast cancer‐specific (BCSS) and overall survival (OS), and investigated the influence of several prognostic factors. Patients with primary T1‐2N0‐2M0 breast cancer, diagnosed between 1999 and 2012, were selected from the Netherlands Cancer Registry. We investigated the 1999–2005 (long‐term outcome) and the 2006–2012 cohort (contemporary adjuvant systemic therapy). Cause of death was derived from the Statistics Netherlands (CBS). Multivariable analyses, per time cohort, were performed in T1‐2N0‐2, and separately in T1‐2N0‐1 and T1‐2N2 stages. The T1‐2N0‐1 stages were further stratified for age, hormonal receptor and HER2 status, adjuvant systemic therapy and comorbidity. In total, 129,692 patients were included. In the 1999–2005 cohort, better BCSS and OS for BCT than mastectomy was seen in all subgroups, except in patients < 40 years with T1‐2N0‐1 stage. In the 2006–2012 cohort, superior BCSS and OS were found for T1‐2N0‐1, but not for T1‐2N2. Subgroup analyses for T1‐2N0‐1 showed superior BCSS and OS for BCT in patients >50 years, not treated with chemotherapy and with comorbidity. Both treatments led to similar BCSS in patients <50 years, without comorbidity and those treated with chemotherapy. Although confounding by severity and residual confounding cannot be excluded, this study showed better long‐term BCSS for BCT than mastectomy. Even with more contemporary diagnostics and therapies we identified several subgroups that may benefit from BCT. Our results support the hypothesis that BCT might be preferred in most breast cancer patients when both treatments are suitable.     

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of thisstudy was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathologicalfeatures of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20%and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001),estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymphnode positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free andoverall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated withER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The levelof Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.     

Menopausal hormone therapy use and long-term all-cause and cause-specific mortality in the Long Island Breast Cancer Study Project

Previous studies have observed a reduced mortality risk associated with menopausal hormone therapy (MHT) use among breast cancer survivors. We sought to clarify whether such association could be explained by tumor heterogeneity, specific causes of death, confounding from comorbidities or health behaviors, and a comparison group of women without breast cancer. We interviewed 1508 women newly diagnosed with first primary breast cancer in 1996 to 1997 (~3 months after diagnosis), and 1556 age-matched women without breast cancer, about MHT use history. The National Death Index was used to ascertain vital status after a median of 17.6 years of follow-up (N = 597 deaths for breast cancer subjects). Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality, and cause-specific HR (cHR) for breast cancer and cardiovascular disease (CVD). The Fine-Gray model was used to account for competing causes of death. Among women with breast cancer, ever vs never MHT use was inversely associated with all-cause (HR = 0.77, 95%CI = 0.62-0.95), breast cancer-specific (cHR = 0.69, 95%CI = 0.48-0.98), and CVD-specific mortality (cHR = 0.57, 95%CI = 0.38-0.85). Difference of the association was observed in breast cancer-specific mortality according to hormone receptor status (negative tumors: cHR = 0.44, 95%CI = 0.19-1.01; positive tumors: cHR = 0.96, 95%CI = 0.60-1.53). Among the comparison group, we observed similar, but more modest inverse associations for all-cause and CVD-specific mortality. MHT use was inversely associated with mortality after breast cancer, even after accounting for competing causes of death and multiple confounders, and was evident among women without breast cancer. Potential heterogeneity by hormone receptor status requires more study.     

Different types of postmenopausal hormone therapy and mammographic density in Norwegian women

Postmenopausal hormone therapy (HT) is associated with increased risk of breast cancer. The HTs used in Scandinavia is associated with higher risk estimates than those used in most other countries. Mammographic density is one of the strongest risk factors for breast cancer, and possibly an intermediate marker for breast cancer. We decided to examine the relationship between use of different types of HT and mammographic density in Norwegian women. Altogether, 1,007 postmenopausal participants in the governmental mammographic screening program were asked about current and previous HT use. Mammograms were classified according to percent and absolute mammographic density. Overall, current users of HT had on average 3.6% higher mean percent mammographic density when compared with never users (p < 0.001). After adjustment for age at screening, number of children and BMI in a multivariate model, women using the continuous estradiol (E(2)) plus norethisterone acetate (NETA) combination had a mean percent mammographic density significantly higher than never users (6.1% absolute difference). Those using the continuous E(2) plus NETA combination had an 4.8% (absolute difference) higher mean percent mammographic density after <5 years of use when compared with never users, while the corresponding number for >or=5 years of use was 7% (p-trend < 0.001). We found similar associations when absolute mammographic density was used as the outcome variable. In summary, our study shows a statistical significant positive dose-response association between current use of the continuous E(2) plus NETA combination and both measures of mammographic density.     

An overview of menopausal oestrogen-progestin hormone therapy and breast cancer risk

Results from the Women's Health Initiative (WHI) trial support findings from observational studies that oestrogen-progestin therapy (EPT) use is associated with an increase in breast cancer risk. We conducted a meta-analysis using EPT-specific results from the Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) pooled analysis and studies published since that report to obtain an overview of EPT use and breast cancer risk. We also assessed risk by histologic subtype of breast cancer, by schedule of the progestin component of EPT, and by recency of use. We estimate that overall, EPT results in a 7.6% increase in breast cancer risk per year of use. The risk was statistically significantly lower in US studies than in European studies - 5.2 vs 7.9%. There was a significantly higher risk for continuous-combined than for sequential EPT use in Scandinavian studies where much higher total doses of progestin were used in continuous-combined than in sequential EPT. We observed no overall difference in risk for lobular vs ductal carcinoma but did observe a slightly higher risk for current vs past EPT use.     

Socioeconomic factors associated with adjuvant hormone therapy use in older breast cancer survivors

BACKGROUND:

The authors sought to identify socioeconomic (SES) factors associated with adjuvant hormone therapy (HT) use among a contemporary population of older breast cancer survivors.

METHODS:

Telephone surveys were conducted among women (ages 65‐89 years) residing in 4 states (California, Florida, Illinois, and New York) who underwent initial breast cancer surgery in 2003. Demographic, SES, and treatment information was collected.

RESULTS:

Of 2191 women, 67% received adjuvant HT with either tamoxifen or an aromatase inhibitor (AI); 71% of those women were on an AI. When adjusting for multiple demographic and SES factors, predictors of HT use were better education (high school degree or higher), better informational/emotional support, and younger age (ages 65‐79 years). Race/ethnicity, income, and insurance coverage for medication costs were not associated with receiving HT. For those on HT, when adjusting for all other factors, women were more likely to receive an AI if they had insurance coverage for some or all medication costs, if they were wealthier, if they had better informational/emotional support, and if they were younger (ages 65‐69 years).

CONCLUSIONS:

The majority of older women in this population‐based cohort received adjuvant HT, and the adoption of AIs was early. The results indicted that providers should be aware that a woman's education level and support system influence her decision to take HT. Given the high cost of AIs, their benefits in postmenopausal women with hormone receptor‐positive breast cancer, and the current finding that women with no insurance coverage for medication costs were significantly less likely to receive an AI, we recommend that policymakers address this issue. Cancer 2011. © 2010 American Cancer Society.     

Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women

OBJECTIVE: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. METHODS: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case-control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. RESULTS: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01-1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97-1.03). CONCLUSIONS: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.