Tamoxifen and toremifene treatment of breast cancer and risk of subsequent endometrial cancer: a population-based case-control study

A population-based case-control study was performed to evaluate the risk of endometrial cancer related to tamoxifen or toremifene treatment. All patients with breast cancer diagnosis since 1980 in Finland who subsequently developed an endometrial cancer by the end of 1995 and 3 matched controls were identified among the 38,000 breast cancer patients of the Finnish Cancer Registry database. Detailed information on treatment of breast cancer and potential confounders was collected from hospital records. The OR for tamoxifen treatment (59 cases), adjusted for significant cofactors (increased risk associated with obesity, low parity and PR positivity) was 2.9 (95% CI 1.8-4.7). The OR for toremifene (3 cases) was 0.9 (95% CI 0.3-3.9). The OR related to adjuvant tamoxifen treatment reached its maximum 2-5 years after the beginning of treatment (OR 5.1, 95% CI 2.1-13), while the OR for tamoxifen used for palliative treatment of advanced breast cancer was especially high after a lag of over 5 years (OR 9.5, 95% CI 2.5-36). The risk increase due to tamoxifen was slightly higher if the age at initiation was below 55, and risk was more pronounced among patients with well-differentiated endometrial cancer than patients with cancers of clinical grades 2 or 3. According to our results, treatment with tamoxifen increases the risk of endometrial cancer. Due to the rare use of toremifene up to the mid-1990s, the risk assessment concerning it was inconclusive.     

Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women: Results from a controlled randomised trial

BackgroundAdjuvant treatment with tamoxifen reduces the risk of contralateral breast cancer in hormone-responsive postmenopausal patients, whereas the effect in premenopausal women has not been fully elucidated. We have therefore studied the effect of tamoxifen on contralateral breast cancer in premenopausal women in a controlled randomised trial.Patients and methodsPremenopausal women (564) with stage II breast cancers were randomised to 2 years of tamoxifen versus control irrespective of oestrogen receptor (ER) and progesterone receptor (PgR) status. The median follow-up for patients not developing a contralateral cancer was 14 years.ResultsIn the control group 35 women, and in the tamoxifen group 17 women, developed a contralateral breast cancer as a primary event. Tamoxifen significantly reduced the risk of contralateral breast cancer in all women regardless of age (hazard ratio (HR) 0.5, p = 0.02). In subgroup analysis the risk reduction was most pronounced in patients <40 years of age (HR 0.09, p = 0.02). A risk reduction was also seen in women 40–49 years of age or ?50 years of age, although in these subgroups this did not reach statistical significance. The reduced risk of contralateral breast cancer was persistent during the whole follow-up time.ConclusionIn this randomised trial, adjuvant treatment using tamoxifen for 2 years reduced the incidence of contralateral breast cancer by 50% in all premenopausal women, and by 90% in women <40 years of age. The effect of tamoxifen was not significantly dependent on time.     

Tamoxifen (Nolvadex) for premenopausal patients with advanced breast cancer

Summary Clinical results of tamoxifen (Nolvadex-ICI) monotherapy in 44 premenopausal women with advanced breast cancer have been reviewed. Objective tumor regression was achieved in 12 (27%) patients and a further 10 (22%) were classified as stabilized. Median duration of response was 12.7 months at the time of analysis. Greatest benefits occurred in soft tissue dominant and receptor-positive tumors, but there was no correlation between tumor response and other clinical manifestations of estrogen deprivation (e.g. menstrual disturbance, hot flushes).The benefits of conventional doses of tamoxifen do not therefore appear to be influenced by menopausal status and compare favorably to achievements reported after surgical oophorectomy.     

Endocrine therapy in premenopausal women with breast cancer: a critical appraisal of current evidence

Nearly 60% of all breast cancer premenopausal women are diagnosed with a hormone receptor positive tumor and, therefore, are candidates for adjuvant hormonal therapy. Treatment with tamoxifen for at least 5 years has been for a long time the standard of care, as it is associated with overall positive clinical outcomes. However, in the last decade, a number of studies on adjuvant endocrine therapy in premenopausal women with hormone receptor positive breast cancer have been published, adding a bulk of evidence to existing knowledge in this field. A critical appraisal of their results appears necessary in order to put the recently collected data into the current framework of treatment, and to discuss the several issues that remain open. Here, we review the most recent evidence on the following: the optimal duration of tamoxifen treatment, results of the studies comparing tamoxifen alone to tamoxifen plus ovarian function suppression (OFS), results of the studies comparing tamoxifen plus OFS to aromatase inhibitors plus OFS.     

Combined effects of goserelin and tamoxifen on estradiol level,breast density,and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial

Background:

This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer.

Methods:

This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and randomly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months. Contralateral BD was also measured at 0, 12, and 18 months.

Results:

Five participants dropped out of the goserelin plus TAM group, and two participants dropped out of the TAM-alone group before initiation of endocrine therapy. The rest of patients received scheduled treatment and 3 years of median follow-up. No serious adverse effects were observed, and only two local recurrences have been observed in these patients. Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group (P<0.05). The endometrium in the goserelin plus TAM group was significantly thinner than that in the TAM-alone group (P<0.05), and women in the TAM-alone group exhibited endometrial thickening over the course of the study. Furthermore, no significant differences in blood lipid levels were reported between the two groups.

Conclusion:

The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level, followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer, which may eventually lead to better outcome in these patients.     

Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study

A diet high in isoflavonoids (soy) is associated with lower breast cancer risk in Asian populations. Due to the low soy intake, dietary lignans may be the more important phytoestrogen class in Western populations. We used a population-based case-control study of breast cancer by age 50 in southern Germany to evaluate the association between dietary intake of different phytoestrogens and premenopausal breast cancer risk. Dietary information was collected from 278 premenopausal cases and 666 age-matched controls, using a validated FFQ. Using multivariate logistic regression, the highest vs. lowest intake quartiles of daidzein and genistein yielded significantly reduced ORs (95% CI) for breast cancer risk of 0.62 (0.40-0.95) and 0.47 (0.29-0.74), respectively. The protective effects of daidzein and genistein were found only for hormone receptor-positive tumors. High intake of other isoflavonoids, e.g., formononetin and biochanin A, as well as the sum of isoflavonoids were not associated with a decrease in risk. Breast cancer risk significantly decreased with a high intake of the plant lignan matairesinol (OR = 0.58, 95% CI 0.37-0.94) but not secoisolariciresinol or the sum of plant lignans. However, both estimated mammalian lignans, enterodiol and enterolactone, were inversely associated with breast cancer risk, with ORs (95% CI) of 0.61 (0.39-0.98) and 0.57 (0.35-0.92), respectively. No effect was found for total phytoestrogen intake. Our results suggest an important role of dietary intake of daidzein and genistein, despite low levels, as well as of matairesinol and mammalian lignans to reduce premenopausal breast cancer risk in this study population.     

Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic

Background:

Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews.

Methods:

All eligible women between 33 and 46 years at ⩾17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews.

Results:

Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others'' experience on beliefs about tamoxifen, tamoxifen as a ‘cancer drug'', and daily reminder of cancer risk.

Conclusions:

Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.     

Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study

Laboratory and epidemiological data have linked vitamin D to breast cancer prevention. Beside dietary intake, endogenous production of vitamin D substantially contributes to a subject's vitamin D status. Most studies, however, have assessed dietary intake only. Although differential effects of vitamin D on premenopausal and postmenopausal breast cancer have been discussed, this is the first study to investigate the association of plasma 25-hydroxyvitamin D [25(OH)D], as indicator of the overall vitamin D status, with breast cancer risk with restriction to premenopausal women only. We used data of a population-based case-control study comprising 289 cases and 595 matched controls. Information on sociodemographic and breast cancer risk factors was collected by questionnaire and plasma 25(OH)D was measured by enzyme immunoassay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. We observed a significant inverse association between breast cancer risk and plasma 25(OH)D concentrations. Compared with the lowest category (<30 nmol/L), the ORs (95% CI) for the upper categories (30-45, 45-60, >or=60 nmol/L) were 0.68 (0.43-1.07), 0.59 (0.37-0.94) and 0.45 (0.29-0.70), respectively (p(trend) = 0.0006). The association was shown to be nonlinear (p(nonlinearity) = 0.06) in fractional polynomial analysis with a stronger effect in women at low plasma 25(OH)D levels, providing some evidence of a threshold effect (at circa 50 nmol/L). The association was stronger in progesterone receptor negative tumors, with suggestive evidence of effect heterogeneity (p(heterogeneity) = 0.05, case-only model). Our findings support a protective effect of vitamin D for premenopausal breast cancer.     

Tamoxifen and fluoxymesterone versus tamoxifen and danazol in metastatic breast cancer — A randomized study

Summary A prospective randomized trial of tamoxifen and fluoxymesterone versus tamoxifen and danazol in metastatic breast cancer was conducted from December 1980 to September 1985. Patients were eligible regardless of site of disease, estrogen receptor status, or age. Sixty-two of sixty-three randomized patients were evaluable for response. Overall response for tamoxifen and fluoxymesterone was 11% with 61% stabilization of disease, versus 12% response rate for tamoxifen and danazol with 59% stabilization. Toxicities with tamoxifen and fluoxymesterone were greater with an increase in masculinization. We conclude that the response rates to the combinations of tamoxifen and fluoxymesterone or tamoxifen and danazol reported are equivalent in this study but that the increased toxicity with tamoxifen and fluoxymesterone would make tamoxifen and danazol the treatment of choice if a combination were to be used.     

Risk factors for premenopausal breast cancer: a case-control study in Uruguay

In order to thoroughly analyze risk factors of breast cancer (BC) in premenopausal Uruguayan women, a case-control study was carried out at the Pereira Rossell Women's Hospital, Montevideo, where 253 incident BC cases and 497 frequency-matched healthy controls were interviewed on menstrual and reproductive story, were administered a short food frequency questionnaire and undertook a series of body measurements necessary to calculate body composition and somatotype. Odds ratio (OR) coefficients were taken as estimates of relative risk derived from unconditional logistic regression. Among the classical risk factors, only the family history of BC in first degree relatives was significantly associated with risk of premenopausal BC (OR=2.20, 95% CI 1.33-3.62). Interestingly, this risk factor was found to be stronger in women of ages >40 (OR=4.05, 95% CI 2.10-7.81), late menarche (OR= 2.39, 95% CI 1.18-4.85), early age for their first delivery (OR=3.02, 95% CI 1.26-7.22), short time between menarche and first delivery (OR=3.22, 95% CI 1.29-8.07), and with high parity (OR=4.10, 95% CI 1.79-9.36), although heterogeneity was detected only for age and parity. High consumption of red meat was positively associated with the disease risk (OR=2.20, 95% CI 1.35-3.60), in the same way as fried foods (OR=1.79, 95% CI 1.12-2.84). Conversely, a high intake of plant foods displayed a protective effect (OR=0.41, 95% CI 0.26-0.65). Except for hypertension (OR=1.55, 95% CI 1.03-2.35), none of the analyzed components of metabolic syndrome were associated to BC risk. Particular increases of risk for premenopausal BC were found for family history in first degree relatives in certain subsets derived from the menstrual-reproductive history. Preventive strategies could broaden their scope if new studies confirm the present results, in view of the limited prevention measures that premenopausal BC currently has.     

Tamoxifen and interferon-beta for the treatment of metastatic breast cancer

Summary It has been demonstrated, both in breast cancer cell lines and in metastatic breast cancer patients with cutaneous lesions that could be biopsied, that treatment with interferon beta (IFN-B) can increase expression of both estrogen (ER) and progesterone receptors (PgR). To evaluate the efficacy and toxicity of the combination of IFN and tamoxifen, 33 metastatic breast cancer patients were treated with the following regimen: IFN-B, 6.0 million units intramuscularly IU 3 times a week for two consecutive weeks followed by IFN-B 6.0 million IU im 3 times a week with concomitant tamoxifen 20 mg orally daily. Patients were pre and postmenopausal with median age of 60 years, median ECOG PS of 0, either ER positive or unknown, and had not received prior hormone therapy for metastatic disease. Overall objective response was observed in 9 (27%) patients. Complete response was observed in 2 cases and partial response in 7 patients. Median duration of response was 7 months (range 2–10). A higher response rate was observed in patients with predominantly soft tissue disease (38%) compared to patients with either dominant bone (18%) or visceral lesions (17%). Toxicity was mild and reversible: low grade fever in 30% of patients and flu-like symptoms in 9% of cases. It appears that IFN-B does not improve the efficacy of tamoxifen in an unselected population of metastatic breast cancer.     

Ovarian cyst formation in patients using tamoxifen for breast cancer

OBJECTIVE: The purpose of this study was to evaluate patient-related parameters that determine ovarian cyst formation in women using tamoxifen for breast cancer. METHODS: A retrospective review of tamoxifen-treated women with breast cancer who were followed up in the outpatient clinic at Ankara Oncology Hospital between January 2002 and December 2004 was performed. Tamoxifen doses and duration, post-treatment menstrual function, adjuvant therapy, ultrasonographic and hormonal [follicle-stimulating hormone and serum estradiol (E(2))] data, details of gynecologic surgical procedure and histopathology were recorded. RESULTS: Twenty-nine of 150 tamoxifen-treated patients (19.3%) had ovarian cysts. Cysts were detected in 28 of 57 pre-menopausal women (49.1%) and 1 of 93 post-menopausal women (1.1%). Patients with ovarian cysts had higher serum E(2) levels compared with patients without cysts (24 versus 345 pg/ml; P < 0.001). Patients with ovarian cysts had <1 year amenorrhoea duration (P < 0.001) compared with the patients without cysts. Adjuvant standard chemotherapy did not have relationship between the development of ovarian cysts. Multivariant analysis showed that cyst development is related to high E(2) levels (P < 0.05). CONCLUSIONS: Patients still having a menstrual cycle during tamoxifen had high risk (58.33%) of developing ovarian cysts. We have described an association between pre-menopausal patients using tamoxifen with high E(2) level and ovarian cyst enlargement.     

Outcomes in patients with primary breast cancer and a subsequent diagnosis of endometrial cancer : comparison of cohorts treated with and without tamoxifen

BACKGROUND: The study compared tumor characteristics and survival in women with breast cancer who subsequently developed endometrial cancer with or without a history of tamoxifen use. METHODS: The British Columbia Cancer Agency registry identified 163 women diagnosed with breast cancer between 1989-1999 who received a subsequent diagnosis of endometrial cancer. Of these, 55% (n = 90) had a history of tamoxifen use. Outcomes analyzed were breast cancer-specific survival (BCSS), endometrial cancer-specific survival (ECSS), and overall survival (OS). RESULTS: Median follow-up was 9.4 years. Distributions of age, menopausal status, body mass index, and comorbidities were similar in the tamoxifen-treated and nontamoxifen cohorts. Proportions of aggressive endometrial cancer subtypes including papillary serous, clear cell, and mixed mullerian tumors were higher in the tamoxifen cohort (28% vs14%, P = .03). Distributions of endometrial cancer grade and stage were similar in the 2 groups (P > .05). Hysterectomy and/or oophorectomy were the primary treatments for endometrial cancer in 99% of patients, with comparable pelvic control rates in the tamoxifen and nontamoxifen groups. At 10 years, patients in the tamoxifen group experienced lower BCSS compared with the nontamoxifen group (89% vs 97%, P = .02). No significant differences in ECSS and OS were observed between the 2 groups (ECSS 82% and 82%, P = .85; and OS 69% v. 66%, P = .85). CONCLUSIONS: In patients with breast cancer who developed a subsequent endometrial cancer, tamoxifen-treated patients had higher proportions of aggressive endometrial cancer subtypes, but almost all cases were amenable to surgery, thus resulting in similar endometrial cancer control and survival when compared with nontamoxifen treated patients.     

Tamoxifen response following no response to orchiectomy in metastatic male breast cancer: a case report

A male patient with advanced breast cancer had no response to orchiectomy but subsequently enjoyed a 17-month partial response to tamoxifen 10 mg B.I.D. His tumor estrogen receptor (ER) protein was 555 fmol protein/ml cytosol. The potential role of ER determinations in the selection of therapy for advanced male breast cancer is discussed.     

A randomized phase II presurgical trial of weekly low-dose tamoxifen versus raloxifene versus placebo in premenopausal women with estrogen receptor-positive breast cancer

Introduction

We previously demonstrated that 1 or 5 mg per day of tamoxifen (T) given for four weeks before surgery reduces Ki-67 in breast cancer (BC) patients to the same extent as the standard 20 mg/d. Given the long half-life of T, a weekly dose (10 mg per week (w)) may be worth testing. Also, raloxifene (R) has shown Ki-67 reduction in postmenopausal patients in a preoperative setting, but data in premenopausal women are limited. We conducted a randomized trial testing T 10 mg/w vs. R 60 mg/d vs. placebo in a presurgical model.

Methods

Out of 204 screened subjects, 57 were not eligible, 22 refused to participate and 125 were included in the study. The participants were all premenopausal women with estrogen receptor-positive BC. They were randomly assigned to either T 10mg/w or R 60 mg/d or placebo for six weeks before surgery. The primary endpoint was tissue change of Ki-67. Secondary endpoints were modulation of estrogen and progesterone receptors and several other circulating biomarkers.

Results

Ki-67 was not significantly modulated by either treatment. In contrast, both selective estrogen receptor modulators (SERMs) significantly modulated circulating IGF-I/IGFBP-3 ratio, cholesterol, fibrinogen and antithrombin III. Estradiol was increased with both SERMs. Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Moreover, a reduction of Ki-67 and a marked increase of sex hormone-binding globulin (SHBG) were observed in the active phenotype.

Conclusions

A weekly dose of tamoxifen and a standard dose of raloxifene did not inhibit tumor cell proliferation, measured as Ki-67 expression, in premenopausal BC patients. However, in the tamoxifen arm women with an extensive phenotype for CYP2D6 reached a significant Ki-67 modulation.     

Diet and ovarian cancer risk: a case-control study in Italy

To assess the dietary correlates of cancer of the ovary, the consumption of a wide range of food groups has been investigated in a case-control study conducted between January 1992 and September 1999 in 4 Italian areas. Cases were 1,031 women with incident, histologically confirmed epithelial ovarian cancer; controls were 2,411 women admitted to the same network of hospitals as the cases for acute, non-malignant and non-gynecological conditions, unrelated to hormonal or digestive tract diseases or to long-term modifications of diet. The subjects' usual diet was investigated through a validated food frequency questionnaire including 78 foods and recipes, then grouped into 18 food groups. Odds ratios (OR), and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models including terms for age, study center, education, year at interview, parity, oral contraceptive use and energy intake. Significant trends of increasing risk emerged for red meat (OR = 1.53 for the highest compared with the lowest quintile of consumption), whereas inverse associations were observed for consumption of fish (OR = 0.51), raw (OR = 0.47) and cooked vegetables (OR = 0.65), and pulses (OR = 0.77).     

The value of high adherence to tamoxifen in women with breast cancer: a community-based cohort study

Background:

Low adherence to adjuvant tamoxifen is associated with worse health outcomes but little is known about the cost-effectiveness of high adherence.

Methods:

We conducted an economic evaluation using data for all women with incident breast cancer between 1993 and 2000 who were subsequently prescribed tamoxifen in the Tayside region of Scotland. Patient-level, lifetime Markov models evaluated the impact of high vs low adherence to tamoxifen using linked prescribing, cancer registry, clinical cancer audit, hospital discharge and death records. Direct medical costs were estimated for each patient and quality-of-life weights were assigned. Recurrence information was collected by case note review and adherence calculated from prescribing records with low adherence classed below 80%.

Results:

A total of 354 (28%) patients had a recorded recurrence and 504 (39%) died. Four hundred and seventy-five (38%) patients had low adherence over the treatment period, which was associated with reduced time to recurrence of 52% (P<0.001). Time to other cause mortality was also reduced by 23% (P=0.055) but this was not statistically significant. For an average patient over her lifetime, low adherence was associated with a loss of 1.43 (95% CI: 1.15–1.71) discounted life years or 1.12 (95% CI: 0.91–1.34) discounted quality-adjusted life years (QALYs) and increased discounted medical costs of £5970 (95% CI: £4644–£7372). Assuming a willingness to pay threshold of £25 000 per QALY, the expected value of changing a patient from low to high adherence is £33 897 (95% CI: £28 322–£39 652).

Conclusion:

Patients with low adherence have shorter time to recurrence, increased medical costs and worse quality of life. Interventions that encourage patients to continue taking their treatment on a daily basis for the recommended 5-year period may be highly cost-effective.     

Diet and ovarian cancer risk: a case-control study in China

This case-control study, conducted in Zhejiang, China during 1999-2000, investigated whether dietary factors have an aetiological association with ovarian cancer. Cases were 254 patients with histologically confirmed epithelial ovary cancer. The 652 controls comprised 340 hospital visitors, 261 non-neoplasm hospital outpatients without long-term diet modifications and 51 women recruited from the community. A validated food frequency questionnaire was used to measure the habitual diet of cases and controls. The risks of ovarian cancer for the dietary factors were assessed by adjusted odds ratios based on multivariate logistic regression analysis, accounting for potential confounding demographic, lifestyle, familial factors and hormonal status, family ovarian cancer history and total energy intake. The ovarian cancer risk declined with increasing consumption of vegetables and fruits but vice versa with high intakes of animal fat and salted vegetables. The adjusted upper quartile odds ratio compared to the lower quartile was 0.24 (0.1-0.5) for vegetables, 0.36 (0.2-0.7) for fruits, 4.6 (2.2-9.3) for animal fat and 3.4 (2.0-5.8) for preserved (salted) vegetables with significant dose-response relationship. The risk of ovarian cancer also appeared to increase for those women preferring fat, fried, cured and smoked food.     

Cumulative exposure to premenopausal obesity and risk of postmenopausal cancer: A population-based study in Icelandic women

Obesity, often assessed at one point in time, is an established risk factor of several types of cancer, however, associations with cumulative exposure to obesity across the life course are not well understood. We investigated the relationship between combined measures of duration and intensity of premenopausal overweight and obesity and the incidence of postmenopausal breast, endometrial, and colorectal cancers in Icelandic women. Body mass index (BMI) trajectories between ages 20 and 50 of 88,809 women from the Cancer Detection Clinic Cohort were predicted using growth curve models. Indicators of overweight and obesity duration and intensity were computed and their association with risk of postmenopausal breast, endometrial, and colorectal cancers was examined using multivariate Cox models for subjects followed-up beyond the age of 50 (n = 67,488). During a mean follow-up of 17 years, incident events of 3,016 postmenopausal breast, 410 endometrial and 987 colorectal cancers were ascertained. Each 0.1 kg/m² per year increase in BMI between ages 20 and 50 was positively associated with risks of postmenopausal breast, endometrium and colorectal cancers with hazard ratios equal to 1.09 (95% Confidence Interval (CI):1.04–1.13), 1.31 (95% CI: 1.18–1.44) and 1.10 (95% CI: 1.00–1.21), respectively. Compared to women who were never obese, cumulative BMI × years of obesity were linearly positively associated with risk of endometrial cancer, whereas the association with breast cancer was initially positive, but leveled off with increasing cumulative BMI × years. Cumulative exposure to obesity may provide additional insights into the etiology of cancer and should be considered in future studies that assess obesity–cancer relationships.     

Lactation and breast cancer risk: a case-control study in Connecticut

In this report, we examined the relationship between lactation and breast cancer risk, in a case-control study of breast cancer, conducted in Connecticut between 1994 and 1998. Included were 608 incident breast cancer cases and 609 age frequency matched controls, aged 30-80 years old. Cases and controls were interviewed by trained study interviewers, using a standardized, structured questionnaire, to obtain information on lactation and other major risk factors. Parous women who reported ever lactation had a borderline significantly reduced risk of breast cancer (OR = 0.83, 95% CI, 0.63-1.09). An OR of 0.53 (95% CI, 0.27-1.04) was observed in those having breastfed more than 3 children compared to those who never lactated. Women having breastfed their first child for more than 13 months had an OR of 0.47 (95% CI, 0.23-0.94) compared to those who never breastfed. Lifetime duration of lactation also showed a risk reduction while none of the ORs were statistically significant. Further stratification by menopausal status showed a risk reduction related to lactation for both pre- and postmenopausal women, while the relationship is less consistent for the latter. These results support an inverse association between breastfeeding and breast cancer risk.