“Coming to Grips” with Chemotherapy-Induced Premature Menopause

Chemotherapy for early stage breast cancer has significantly improved survival outcomes but is associated with ovarian toxicity, resulting in early menopause for many premenopausal women. A qualitative study was conducted that generated a grounded theory explaining how women carried on with life in response to breast cancer and menopause. My purpose in this article is to describe three distinct types of responses from women in that study: making the best of it, struggling and barely noticing. The degree of menopausal symptom distress and perceived level of preparation for the menopause experience had the greatest influence on the type of response.     

Combined effect of childbearing, menstrual events, and body size on age-specific breast cancer risk

Pike et al. (Nature 1983;303:767-70) and Moolgavkar et al. (JNCI 1980;65:59-69) proposed quantitative theories for the effect on age-specific breast cancer risk of ages at menarche, first childbirth, and menopause. Here the incidence rate functions predicted by these theories are fit to data for 1,884 women of all ages with breast cancer and 3,432 matched controls admitted to San Francisco Bay area hospitals in 1970-1977. A third function describing age-specific breast cancer risk based on the timing of childbearing and menstrual events is presented, and its fit to the data is compared with that of the functions of Pike et al. and Moolgavkar et al. None of the three fully accounted for the protective effects of early age at first childbirth in premenopausal women or of early age at menopause in parous postmenopausal women. To account for the effects of total parity and body mass (Quetelet) index on risk of breast cancer occurrence, the authors developed a fourth incidence rate function by extending the third. Goodness of fit to the data of the fourth function is demonstrated. Age-specific relative risks of breast cancer according to childbearing, menstrual events, and body size are estimated from the fourth function. The main qualitative findings are that 1) the protective effects of late menarche and of early first full-term pregnancy are greater in premenopausal than in postmenopausal women; 2) first full-term pregnancy initially boosts the level of risk, but incidence rates increase with age more slowly thereafter; 3) among the parous, multiparity is protective both in premenopausal and postmenopausal women, regardless of age at first full-term pregnancy; 4) both nulliparous and lean women are more protected by early menopause than are parous and overweight women; 5) increased body mass index is protective before, but detrimental after, menopause; and 6) postmenopausal incidence rates increase with age more rapidly among overweight than among lean women.     

Cognitive behavioral therapy and physical exercise for climacteric symptoms in breast cancer patients experiencing treatment-induced menopause: design of a multicenter trial

Background  

Premature menopause is a major concern of younger women undergoing adjuvant therapy for breast cancer. Hormone replacement therapy is contraindicated in women with a history of breast cancer. Non-hormonal medications show a range of bothersome side-effects. There is growing evidence that cognitive behavioral therapy (CBT) and physical exercise can have a positive impact on symptoms in naturally occurring menopause. The objective of this study is to investigate the efficacy of these interventions among women with breast cancer experiencing treatment-induced menopause.     

Breast cancer in two populations with different levels of risk for the disease

Caucasian women in Hawaii have a higher risk for breast cancer than women of Japanese ancestry. In order to determine to what extent known risk factors account for the difference in risk between the two groups, a case-control study was done from 1975 to 1980. A total of 183 Japanese and 161 Caucasian breast cancer cases were interviewed along with their respective controls. The findings suggested that a positive history of benign breast disease, a family history of breast cancer, late menopause, late age at first childbirth and early age at menarche did not fully account for the difference in breast cancer risk between Caucasian and Japanese women in Hawaii. Attention needs to be focused on other factors that are under environmental influence.     

Intervention with a low-fat, high-carbohydrate diet does not influence the timing of menopause

BACKGROUND: Later age at menopause is associated with a greater risk of breast cancer. Dietary factors may at least partially influence breast cancer risk through an effect on the age at menopause. OBJECTIVE: We studied the effect of a low-fat, high-carbohydrate (LFHC) dietary intervention on the timing of menopause in women with greater risk of breast cancer. DESIGN: The study population included participants from an LFHC dietary intervention trial for the prevention of breast cancer in women with extensive mammographic density, a strong risk factor for breast cancer. Women who were premenopausal at baseline (n = 2611) were followed for an average of 7 y for menopause. Survival analysis was used to compare the time to menopause between the LFHC and control groups and to assess other factors associated with age at menopause. RESULTS: The LFHC intervention did not affect the time to natural menopause overall (P = 0.72 for log-rank test comparing study groups; n = 699 events). An observed interaction between study group and baseline body mass index (BMI; P = 0.01) indicated that the intervention group experienced earlier menopause than did the control group when BMI was low and that a higher BMI was associated with later menopause in the intervention group only. Greater parity, weight, and education were associated with later menopause, and greater age at first birth and baseline smoking were associated with earlier menopause. CONCLUSIONS: Overall, the LFHC dietary intervention did not influence the timing of menopause. Factors associated with age at menopause in this population were consistent with those reported in other populations.     

An epidemiologic study of breast cancer

A case-control study has been conducted in four areas of Canada in which 400 cases of breast cancer matched by age and marital status with neighborhood controls were administered medical and dietary questionnaires. The study is suggestive of an increased risk of breast cancer in post-menopausal women with younger age at menarche and an increased risk with delay of age at natural menopause. No protective effect of early age at first pregnancy was demonstrated in either pre- or post-menopausal women. An increased frequency of pregnancies of four months duration or less was found in cases compared to controls and a greater frequency in pre-menopausal cases compared to controls of a history of irregular menstrual periods. In pre-menopausal women no association has been found between increased height and weight as risk factors for breast cancer. For post-menopausal women, however, a weak association with increased height has been found, while a strong association with increased weight both at the time of menopause and the 12 months preceding diagnosis has ben confirmed.     

Secular trends in the distributions of the breast cancer risk factors--menarche, first birth, menopause, and weight--in Hiroshima and Nagasaki, Japan

The results of a mail survey completed by approximately 21,000 female atomic bomb survivors in Hiroshima and Nagasaki in 1970 are studied with respect to menarche, first birth, menopause, and weight. These known risk factors for breast cancer can be used to explain some but not all of the differences in Japanese and US breast cancer rates. The results for age at menarche are the most striking, with the presence of a strong secular trend. The average age at menarche in Japan was observed to decrease from 16.4 years for women born in 1902 to 14.4 years for women born in 1942. However, a temporary increase was observed in women whose menarche was expected to occur during the war years of the early 1940s. Differences between US and Japanese women were also observed in age at first birth and nulliparity rates. Age at menopause was similar for the two groups, although US women have a considerably higher rate of surgically induced menopause. Within each birth cohort, it is shown that body weight is negatively correlated with age at menarche and positively correlated with age at menopause.     

Misclassification bias related to definition of menopausal status in case-control studies of breast cancer.

It is often assumed, but has not been consistently observed, that some characteristics of reproductive history are specifically related to breast cancer of pre- or postmenopausal onset. To determine whether inconsistent reports may be due to differences in definition of menopause, we computed the relative odds (RO) of breast cancer for nulliparity, age at first live birth, family history of breast cancer and prior history of benign breast disease, separately in pre- and postmenopausal women, using seven different definitions of menopause. Results show that (i) relative odds of breast cancer and their confidence intervals may vary according to definitions of menopause; (ii) age-based definitions of menopause are associated with moderate differential misclassification bias between cases and controls; (iii) nulliparity, late age at first birth and family history of breast cancer seem to be specific risk factors for pre- but not postmenopausal breast cancer when cutoff for menopausal status is 10 years or more after last menses; and (iv) when information on menstrual history is not available, 50 years of age may be the best proxy for all menses-based definitions of menopause. We conclude that inconsistent findings on the effect of menopausal status in the association of breast cancer with some reproductive factors are partly due to statistical imprecision and differential misclassification bias associated with different age-based or menses-based definitions of menopause. Researchers should either test whether their conclusions hold using several definitions of menopause or give a biological rationale for the choice of a given definition of menopause.     

A prospective study of reproductive, familial and socioeconomic risk factors for breast cancer using NHANES I data

Risk factors for breast cancer in a cohort of women who participated in the first National Health and Nutrition Examination Survey (NHANES) and its followup epidemiologic survey were examined. The analytic cohort consisted of 122 breast cancer cases and 7,304 noncases, with a median followup time of 10 years. We found no appreciable increase in risk among women who reported their onset of menarche as occurring before the age of 13 compared with those reporting onset at ages 13 and older. Breast cancer risk was progressively elevated with increasing age at first live birth (test for trend, P less than 0.007). The number of children born to a woman did not influence risk, but the data suggested an increased risk for nulliparous women. A family history of breast cancer in a first-degree relative was the strongest predictor of risk for this cohort of women, with relative risks of 2.2 and 2.4 associated with a mother or sister affected with breast cancer, compared with women having no family history. The age of natural menopause had little influence on breast cancer risk, and the data suggested a slight protective effect of early surgical menopause. Higher education (compared with less than a high school education) was associated with an increased risk in this cohort of women (relative risk (RR) = 2.1; 95 percent confidence interval (CI) = 0.9-5.1). These results (a) confirm the importance of some well-recognized risk factors for breast cancer in a cohort of women, followed prospectively for 10 years, and perhaps more importantly, (b) uniquely provide risk estimates on a probability sample of women in the United States.     

Data analysis methods and the reliability of analytic epidemiologic research

Publications that compare randomized controlled trial and cohort study results on the effects of postmenopausal estrogen-plus-progestin therapy are reviewed. The 2 types of studies agree in identifying an early elevation in coronary heart disease risk, and a later developing elevation in breast cancer risk. Effects among women who begin hormone therapy within a few years after the menopause may be comparatively more favorable for coronary heart disease and less favorable for breast cancer. These analyses illustrate the potential of modern data analysis methods to enhance the reliability and interpretation of epidemiologic data.     

Polycystic ovaries and the risk of breast cancer

Data from a case-control study that was conducted between 1980 and 1982 were analyzed to investigate the possible association between polycystic ovaries and the risk of breast cancer. The multicenter, population-based study included in-home interviews with 4,730 women with breast cancer and 4,688 control women aged 20-54 years. The age-adjusted odds ratio for breast cancer among women with a self-reported history of physician-diagnosed polycystic ovaries was 0.52 (95% confidence interval 0.32-0.87). The inverse association was not an artifact of infertility, age at first birth, or surgical menopause. Because women with this syndrome have abnormal levels of certain endogenous hormones, the observation of a low risk of breast cancer in this group may provide new insights into hormonal influences on breast cancer.     

Age at natural menopause and breast cancer risk: the effect of errors in recall

Many case-control studies of breast cancer have reported estimates of relative risk of approximately 1.9 for menopause after 54 years of age when compared with menopause before 45 years of age. These estimates may be biased towards unity because of errors in recall of a woman's age at menopause. This paper investigates the magnitude of error associated with self-classification of women into categories of age at menopause by using personal interview and medical record data of 67 control women from a case-control study of breast cancer conducted in two retirement communities near Los Angeles in 1977-1978. These estimates of "misclassification" error are combined with various sets of "true" relative risks to yield "observable" relative risks. It is demonstrated that the relative risks associated with various age at menopause groups are likely to range from 1-3.4 rather than 1-1.9 as has been reported in the literature.     

Factors Modifying the Association Between Hormone-Replacement Therapy and Breast Cancer Risk

Objectives: Hormone-replacement therapy (HRT) is an established risk factor for breast cancer. HRT users are different from non-users with respect to socio-economic and other characteristics. There may be women where the HRT-related risk could be modulated by other factors.Methods: We conducted a population-based case–control study with 688 breast cancer cases and 724 controls to characterize HRT users and to estimate odds ratios (OR) and 95% confidence intervals (CI) for HRT use and potentially risk modifying factors. Results: In women aged 50 years and older, 58% of controls and 61% of cases ever used HRT. Among women in natural menopause, HRT use for 10 years and more years was associated with an increased breast cancer risk (OR 1.79, 95% CI, 1.12–2.87), but not among women in surgical menopause (OR 0.61, 95% CI, 0.09–4.17). In the subgroup of women with a positive family history of breast cancer, each year of HRT use increased the risk by 1.22 (95% CI, 1.02–1.47). Another subgroup comprised women with at least 10 diagnostic mammograms (OR 4.04, 95% CI, 1.10–14.81 for using HRT 10 or more years).Conclusions: Long-term HRT use was associated with a breast cancer risk in women with natural menopause. Our findings suggest that this risk may be increased in women with a positive family history of breast cancer and in women who received frequent diagnostic mammographic screens.     

Conjugated equine estrogens and breast cancer risk in the Women's Health Initiative clinical trial and observational study

The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.     

Inverse association between risk factors for benign and malignant breast lesions.

The purpose of the present study was to compare the risk of breast cancer and the risk of benign breast disease using known risk factors for breast cancer. The series was taken during breast cancer screening of women aged 41-60 in an industrial city in Finland. 158 breast lesions were diagnosed, 27 of which were malignant. Women with breast disease and 534 controls were interviewed to obtain epidemiological data. The prevalence of benign lesions decreased after menopause but the prevalence of carcinomas was essentially the same over the age span 41-60. Several risk factors for breast cancer, such as selected reproductive and hormonal characteristics, were not associated with the risk of benign breast disease. Thus it was concluded that benign and malignant breast lesions are not associated in general, and the decrease in the prevalence of benign breast lesions after menopause is more likely to be due to regression than to transition to carcinoma.     

Effect of long-term weight gain on the risk of breast cancer across women’s whole adulthood as well as hormone-changed menopause stages: A systematic review and dose–response meta-analysis

Adult weight gain is a good indicator of excess body fatness for breast cancer risk. However, little is known about the effect of weight gain during other special periods in women’s lifetime. A publication search in PubMed and Embase through April 2020 was conducted. A primary meta-analysis comparing the highest and lowest category and a secondary meta-analysis based on dose–response meta-analysis were performed to calculate risk estimates with 95% confidence intervals using a random-effects model. For postmenopausal breast cancer, the relative risk for highest vs. lowest category of adult weight gain and weight gain since menopause were 1.55 and 1.59 (RR = 1.55, 95% CI: 1.40, 1.71; RR = 1.59, 95% CI: 1.23, 2.05). For per 5 kg increase in adult weight gain, the summary RR of postmenopausal breast cancer was 1.08 (RR = 1.08, 95% CI: 1.07, 1.09), which is much stronger in Asian women (RR = 1.34, 95% CI: 1.22, 1.47). There was no significant finding among premenopausal women (RR = 1.00, 95% CI: 0.83, 1.21). Same as adult weight gain, weight gain since menopause might be an equivalent predictor for postmenopausal breast cancer risk. More studies are warranted to confirm the magnitude of this association further.     

内蒙古2万例体检女性乳腺疾病患病率和致病因素分析

目的 了解内蒙古地区女性乳腺疾病发病情况和主要致病因素,探讨包括乳腺癌在内的乳腺疾病与月经初潮年龄、绝经年龄、人工流产史、饮食习惯等因素的关系,为预防和早期发现女性乳腺疾病提供依据.方法 采用《乳腺病基本情况调查表》对2009-09～2012-09在内蒙古地区不同医院进行体检的18～78岁女性进行问卷调查,建立Access数据库,分析内蒙古地区20000例体检女性乳腺疾病的发病情况和主要致病因素.结果 20000例体检女性中患有乳腺疾病7427例,患病率为37.14％.其中乳腺增生症6480例,占32.40％,患病率最高;乳腺癌的患病率为0.18％;乳腺疾病的发病与月经初潮年龄、绝经年龄、人工流产史、饮食习惯等因素有关.结论 内蒙古地区女性乳腺疾病患病率较高,以乳腺增生为主;月经初潮年龄早、绝经年龄晚、多次人工流产、高脂饮食等是乳腺疾病的致病因素;通过健康体检可做到对乳腺疾病,特别是乳腺癌的预防及早发现、早治疗,对降低乳腺疾病患病率,提高妇女健康水平具有重要的意义.     

A study of breast cancer in Irish women.

In a study of 100 women with breast cancer and 200 unaffected women the epidemiological characteristic of breast cancer most commonly described--namely, an excess of nonparous women among cases when compared with controls, was not observed. It is suggested that two factors, a dearth of first births born to mothers under 20 years of age and an unusually high proportion of first births when aged 30 years or more, are responsible for this finding. No association was found between breast cancer and socioeconomic status, marital status, age at marriage, age at first pregnancy, parity, or age at menarche. Significant associations with breast cancer included age at natural menopause, hysterectomy, and breast trauma. These findings are discussed.     

A study of breast cancer in Irish women.

In a study of 100 women with breast cancer and 200 unaffected women the epidemiological characteristic of breast cancer most commonly described--namely, an excess of nonparous women among cases when compared with controls, was not observed. It is suggested that two factors, a dearth of first births born to mothers under 20 years of age and an unusually high proportion of first births when aged 30 years or more, are responsible for this finding. No association was found between breast cancer and socioeconomic status, marital status, age at marriage, age at first pregnancy, parity, or age at menarche. Significant associations with breast cancer included age at natural menopause, hysterectomy, and breast trauma. These findings are discussed.     

Cigarette smoking and the risk of breast cancer

The authors examined the relation between cigarette smoking and breast cancer in the Centers for Disease Control Cancer and Steroid Hormone Study, a multicenter, population-based case-control study. The study compared 4,720 women aged 20-54 years with newly diagnosed breast cancer identified through population-based tumor registries with 4,682 women randomly selected from the same geographic areas. Women who reported ever smoking cigarettes had a risk of breast cancer of 1.2 (95 percent confidence interval 1.1-1.3) compared with never smokers. There was no consistent dose-response pattern with any measure of smoking (pack-years of smoking, average number of cigarettes per day, or total years smoked) and little difference in risk between current and former smokers. There was some variation in risk by age, with slightly higher risk estimates for younger women than for older women. Although current smokers had an earlier natural menopause than did never smokers, the authors found no evidence of a protective effect of cigarette smoking on breast cancer risk. These findings suggest that the risk of breast cancer in women who smoke is the same as, or perhaps slightly higher than, women who have never smoked.