Pregnancy and breast cancer: A possible explanation for the negative association

We propose that pregnancy protects against breast cancer, in part, because it results in excretion of lipophilic carcinogens by the mother through the fetal fat and vernix caseosa. We review several lines of epidemiologic and toxicologic evidence in support of this idea, including concordances between known or suspected risk factors for cancer of the female breast and known or suspected risk factors for increased body burdens of lipophilic carcinogens.     

A review of the etiology of breast cancer.

It is important that physicians be aware of the current theories on the etiology of breast cancer. This article reviews some of the more probable etiologic factors of breast cancer.     

A systematic review and meta-analysis of the association between HOTAIR polymorphisms and susceptibility to breast cancer

IntroductionMany studies are drawing attention to the associations of HOTAIR polymorphisms and susceptibility to breast cancer, while the results remain inconsistent. We conducted a meta-analysis on the association of four common HOTAIR polymorphisms with breast cancer susceptibility.Material and methodsEligible published articles were searched in PubMed, Embase, Cochrane library databases and Web of Science databases up to July 2019. Odds ratios with 95% confidence intervals were used to identify potential links between lncRNA HOTAIR polymorphisms and the risk of breast cancer.ResultsOur results showed no significance in all genetic models of all four SNPs. Pooled analyses detected crucial links between the rs1899663 polymorphism and decreased susceptibility to breast cancer in five genetic models rather than the dominant model in the hospital-based control subgroup. For the rs920778 polymorphism, we found that it significantly decreased breast cancer risk under recessive, homozygous and heterozygous models within the west Asian subgroup and increased breast cancer risk under allele and dominant models within the East Asian subgroup. Additionally, rs920778 polymorphism decreased breast cancer risk under recessive and heterozygous models in the hospital-based control subgroup. However, no significant association was observed between the rs4759314 polymorphism and breast cancer risk in overall and stratified analyses. For rs12826786 polymorphism, it was greatly associated with decreased breast cancer risk under recessive, homozygous and heterozygous models in the hospital-based control subgroup.ConclusionsHOTAIR rs920778, rs1899663 and rs12826786 polymorphisms may contribute to breast cancer susceptibility.     

性激素水平与女性乳腺癌的相关性研究

目的：本研究旨在探讨本地区部分女性性激素水平与乳腺癌发生的关系,为高危人群的发现、疾病控制策略的制定以及针对性的药物研发提供科学依据。方法：2013年1月至2015年1月,本研究从延安大学附属医院收集研究对象,按照乳腺疾病状态分为乳腺癌组(72例)和健康对照组(93例)。数据处理使用SPSS22.0,比较研究对象的一般资料及性激素水平差异,同时按照四分位数将各激素水平分为四个层次,以P25组水平作为参照组,进行非条件Logistic回归分析。结果：按照四分位数将各激素水平分为四个层次,与P25组睾酮水平相比较,P25~P50组的黄体期女性其乳腺癌风险有上升;P75组的卵泡期及绝经后期女性其乳腺癌风险显著上升。以P25组雌二醇水平为参照组, P50~P75组的黄体期女性其乳腺癌风险有上升;P75组的卵泡期、黄体期及绝经后期女性其乳腺癌风险显著上升。与P25组孕酮水平相比较,P50~P75组的黄体期女性其乳腺癌风险有上升;P75组的黄体期女性其乳腺癌风险显著上升。同时对不同暴露水平进行趋势卡方检验的结果显示,绝经后期女性其乳腺癌发生风险随着睾酮水平的上升显著增加(Ptrend=0.027)。卵泡期、黄体期及绝经后期女性乳腺癌发生风险随着雌二醇水平的上升显著增加(Ptrend=0.032、0.039、0.041)。黄体期女性其乳腺癌的发生风险随着孕酮水平的上升显著增加(Ptrend=0.011)。结论：通过对本地区部分女性的调查分析,发现绝经后期女性乳腺癌发生风险随着睾酮水平的上升显著增加;卵泡期、黄体期及绝经后期女性乳腺癌发生风险随着雌二醇水平的上升显著增加;黄体期女性其乳腺癌的发生风险随着孕酮水平的上升显著增加。     

Fertility drugs and the risk of breast cancer.

Several studies have investigated the possible relationship between fertility drugs and the risk of breast cancer. To provide further information on this issue, we analysed data from a case control study, conducted in Northern Italy between 1983 and 1991. Trained interviewers identified and questioned 3415 cases (women aged 23-74 years with histologically confirmed breast cancer) and 2916 controls (women aged 21-74 years admitted to the same hospitals for diseases other than malignant, hormonal or gynaecological conditions). Fifty (1.5%) cases and 53 (1.8%) controls reported any history of infertility; the corresponding multivariate odds ratios (OR) of breast cancer was 0.8 [95% confidence interval (CI) 0.5-1.1]. Sixteen (0.5%) cases and 11 (0.4%) controls reported ever using fertility drugs; the corresponding OR was 1.2 (95% CI 0.5-2.6). Allowance for potential confounding factors did not markedly modify these estimates. In conclusion, this study provides reassuring evidence on the absence of an association between fertility drug treatment and breast cancer risk.     

A patient with prostate cancer and multiple myeloma-diagnostics and possible association of both diseases

In this report, we describe a case of a patient with prostate cancer and multiple myeloma as the second metachronous malignant disease. To our knowledge, synchronous occurrence of bone marrow prostate cancer metastases and multiple myeloma-as it was found in the clinical disease course of our patient-has not been documented in the literature. Among other diagnostic procedures, cytomorphology and immunocytochemistry analyses contribute to detection of metastases of epithelial cells and synchronous plasma cell proliferation in bone marrow. Occurrence of multiple myeloma and prostate cancer in our patient adds to other similar reports and points to possible association between both diseases and also to other factors involved in the development of a second malignant disease. Further studies are needed to confirm and clarify this association, because prostate cancer is a relatively common malignant disease.     

Dexamethasone suppression test and selection of antidepressant medications

Endogenous depressives with abnormal dexamethasone suppression tests (DSTs) respond better to somatic antidepressant treatments than those with normal DSTs. Whether the DST also aids in the selection of specific antidepressants has not been determined. A pilot report suggested that patients with abnormal DSTs might be noradrenaline-deficient and respond preferentially to imipramine or desipramine, whereas those with normal DSTs might be serotonin-deficient and respond best to amitriptyline or clomipramine. Attempting to replicate this observation, we studied 26 patients diagnosed with Research Diagnostic Criteria as major depressive disorder, endogenous subtype, and with DSM-III as having melancholia. All were drug-free during baseline evaluation. All had abnormal DST results, with post-dexamethasone plasma cortisol levels exceeding 5 μg/dl. We treated subjects with either imipramine or amitriptyline and compared clinical response with weekly Hamilton Depression Rating Scales, completed by raters blind to both DST results and the research question. Therapeutic plasma levels were documented. We found no significant differences in treatment response between the subgroups. Twenty of the 26 subjects did well. The imipramine-treated group failed to have either earlier response or better final outcome. These data fail to replicate suggestions that DST results assist in the selection of either imipramine or amitriptyline.     

Family history and risk of breast cancer.

The risk of breast cancer in first degree relatives of patients with breast cancer can be derived from family history and is dependent upon the age at diagnosis in the index patient. For the relatives of index patients older than 55, the relative risk is 1.57, if less than 55 the relative risk is 2.29, and 3.85 if less than 45 (95% confidence limits 0.83 to 2.68, 1.18 to 4.01, and 1.67 to 3.85, respectively). First degree relatives of patients with bilateral breast cancer have a 6.43-fold increase in risk (95% confidence limits 1.32 to 18.77). The genetic contribution to overall lifetime liability to breast cancer in the relatives declines rapidly with increasing age of onset of breast cancer in the index patient from 37% at 20 years to 8% by 45 years. This information can be used in clinical practice for counselling and the establishment of screening programmes.     

A possible link between the pubertal growth of girls and breast cancer in their daughters.

One hypothesis for the origins of breast cancer is that it is initiated by exposure of developing breast tissue in utero to maternal sex hormones. The sex hormone profile is established at puberty, when it regulates growth of the pelvic bones. The pubertal growth of girls is characterized by broadening and rounding of the pelvis. The maximal width between their iliac crests, the intercristal width, increases more rapidly than in boys. We hypothesized that higher sex hormone concentrations at puberty produce larger intercristal widths, and these are markers of increased breast cancer risk in the next generation. We followed up 6,370 women who were born in Helsinki during 1934-1944, and whose mothers' pelvic bones were measured during routine antenatal care. Women whose mothers had large intercristal widths had higher rates of breast cancer. In those born at or after 40 weeks gestation, the hazard ratio for breast cancer was 3.7 (95% CI: 2.1-6.6) if their mother's intercristal width was greater than 30 cm. Among women born to multiparous mothers this hazard ratio rose to 7.2 (3.4-15.4). Hazard ratios for breast cancer were also higher in the daughters of mothers with round iliac crests. Pelvic bone measurements which increase similarly in girls and boys at puberty did not predict breast cancer. We conclude that the intercristal width, and the roundness of the iliac crests, are markers of mothers' sex hormones, and postulate that high concentrations cause genetic instability in differentiating breast cells in their daughters in utero.     

A possible genetic association between PROP-tasting and alcoholism.

Fifty-five young adult subjects and their parents were classified as alcoholic or nonalcoholic based on a standardized questionnaire (the MAST) filled out by the subjects. Subjects' thresholds for detection of 6-n-propylthiouracil (PROP; a PTC-like compound) were determined with the experimenter blind to MAST responses. There was a significantly higher proportion of nontasters of PROP among children of alcoholics than among children of nonalcoholics. There was no relationship between the child's alcoholism status and ability to taste PROP. These results are inconsistent with the view that excessive use of alcohol causes the association between nontasting and alcoholism and are consistent with the view that there is a genetic association between PROP/PTC-tasting and alcoholism.     

Glycoprotein CD44 expression and its association with survival in breast cancer.

To investigate the clinical significance of CD44 expression (lymphocyte-homing receptor) in adenocarcinoma, deparaffinized sections from 198 female breast carcinomas were stained with Hermes-3 MoAb for CD44 glycoprotein. In 16% of the cancers most (> or = 90%) of the cancer cells stained positively for CD44, whereas the rest of the cancers were either heterogenous (46%) or negative (38%) in CD44 staining. Cancers with > 50% CD44 positive cells were more often poorly differentiated (grade 3) than those with < or = 50% positive cells (38 vs. 19%, P = 0.006), they had higher mitotic counts (P = 0.04), and were more often estrogen receptor negative (52 vs. 31%, P = 0.01). Among ductal not otherwise specified cancers and node-positive cancers strong CD44 expression was associated with poor outcome (P = 0.05 and 0.02, respectively). However, CD44 expression was not an independent prognostic factor in these subgroups in a multivariate analysis. Unlike in lymphomas the unfavorable prognosis associated with CD44 expression may not be explained by the greater metastatic potential of CD44-positive cells, because the difference in mortality between the groups appeared to diminish with time, and CD44 positivity was associated with aggressive histological features.     

Use of alternative medicine by women with early-stage breast cancer.

BACKGROUND: We analyzed the use of alternative medicine by women who had received standard therapy for early-stage breast cancer diagnosed between September 1993 and September 1995. METHODS: A cohort of 480 patients with newly diagnosed early-stage breast cancer was recruited from a Massachusetts statewide cohort of women participating in a study of how women choose treatment for cancer. Alternative medical treatments, conventional therapies, and health-related quality of life were examined. RESULTS: New use of alternative medicine after surgery for breast cancer was common (reported by 28.1 percent of the women); such use was not associated with choices about standard medical therapies after we controlled for clinical and sociodemographic variables. A total of 10.6 percent of the women had used alternative medicine before they were given a diagnosis of breast cancer. Women who initiated the use of alternative medicine after surgery reported a worse quality of life than women who never used alternative medicine. Mental health scores were similar at base line among women who decided to use alternative medicine and those who did not, but three months after surgery the use of alternative medicine was independently associated with depression, fear of recurrence of cancer, lower scores for mental health and sexual satisfaction, and more physical symptoms as well as symptoms of greater intensity. All groups of women reported improving quality of life one year after surgery. CONCLUSIONS: Among women with newly diagnosed early-stage breast cancer who had been treated with standard therapies, new use of alternative medicine was a marker of greater psychosocial distress and worse quality of life.