Progestogens and risk of breast cancer: a link between bone and breast?

This article reviews the data supporting the role of receptor activator of the nuclear factor kappa (RANK) and its ligand, RANKL, in progestogen-induced breast cancer. Both experimental and clinical studies have been included. The expression of both RANK and RANKL has been described in epithelial cells of both mice and humans. Experiments of gain and loss of function in mice have shown that RANK/RANKL mediate alveologenesis during pregnancy or the estrous cycle. Moreover, the participation of the RANK/RANKL has been detected in models of breast carcinogenesis associated with progestogens-like medroxyprogesterone acetate. Recent clinical studies have found that the expression of RANK is associated with parameters of aggressiveness of the tumor.     

Genetic polymorphisms of cytochrome P450c17α (CYP17) and progesterone receptor genes (PROGINS) in the assessment of endometriosis risk

We designed the present study in order to evaluate the eventual role of polymorphisms in the genes encoding cytochrome P450c17α (CYP17) and the progesterone receptor (PROGINS) as risk factors for endometriosis development. Eligible cases consisted of 121 women with surgically confirmed endometriosis who underwent treatment in a hospital in São Paulo, Brazil during the period from September 2003 to September 2005. The 281 controls were participants with normal gynecological as well as pelvic ultrasound evaluation, who did not have any gynecological conditions during their reproductive lives such as pelvic pain and/or dyspareunia nor infertility history. Genomic DNA was obtained from buccal cells and processed for DNA extraction using the GFX DNA extraction kit (GE Healthcare). The CYP17 (?34T→C) polymerase chain reaction–restriction fragment length polymorphism assay has been described previously, as has the progesterone receptor polymorphism (PROGINS) detection assay. PROGINS heterozygosis genotype frequencies were shown to be statistically higher in endometriosis cases compared with controls. On the other hand, differences in the CYP17 polymorphism (?34T → C) frequencies were not even close to significance (p = 0.278) according to our findings.     

Progestins and risk of breast cancer. Much ado about nothing?

In vivo and in vitro studies; epidemiological and statistical publications concerning a possible carcinogenic effect of progesterone--and progestins--raise a question mark. Too many contradictions exist in experimental and clinical studies. A very small increased risk of breast cancer with estrogen therapy has been shown; however bias are often present. It is not clearly demonstrated that the adjunction of progestin to estrogen significantly increases the risk, nor that it brings about a protective effect. Some recent works seem to indicate that continuous estroprogestin replacement therapy might be deleterious, while a sequential regimen would be not. This is to be confirmed. The results of the Women's Health Initiative Study have been analyzed. The data and conclusions of the medical literature should be interpreted very cautiously.     

Fibroadenomas of the breast: is there any association with breast cancer?

PURPOSE: The experience of our Breast Unit in the diagnosis and treatment of fibroadenomas is presented in this retrospective study, focusing specifically in cancer development within these common benign tumors of young age. MATERIAL-METHODS: 310 women with histologically verified breast fibroadenomas who had surgical management in our Unit over the last 14 years were included in the study. RESULTS: Most of them (n: 255) presented with palpable lesions and had triple assessment preoperatively, while the remaining 55 had nonpalpable lesions and underwent needle-wire localization biopsies. Nine cases had cancer development, usually in situ, within the fibroadenomas (2.9%). CONCLUSION: Coexistence of fibroadenomas and breast cancer is relatively rare, but it should not be ignored by breast surgeons, and patients should be properly informed.     

Do there still exist risk factors for breast cancer?

Objectives

To evaluate the risk factors associated with a breast cancer, and to compare the proportion of women at high and low risk for developing breast cancer.

Patients and methods

Retrospective study among 194 women with breast cancer between January 2007 and December 2008 in the Obstetrics, Gynaecology and Reproductive Medicine department of the Amiens’ University hospital.

Results

Concerning all the series, only age, overweight and family antecedents seem risk factors of breast cancer. The proportion of women in the low-risk group (12.3%) is not significantly different from that of the high-risk group (18.5%). In the low-risk group, the factors which seem to influence a breast cancer are those in connection with high levels of estrogens (early age of the first menstruation, late age of the menopause and oral contraceptive use) and the smoke habitus; whereas in the high-risk group, the factors are the nulliparity and the absence of breast feeding.

Discussion and conclusions

One finds in this series a part only of the known risk factors of breast cancer; and the proportion of women at low risk (12.3%) is comparable with that at high risk (18.5%). This study shows the relative weight of the various risk factors of breast cancer, at a time when its prevalence reached 10%.     

Mondor's disease of the breast: is there any relation to breast cancer?

Ten cases of Mondor's disease of the breast (9 females, 1 male) are described. The diagnosis was based mainly on clinical examination, while breast imaging, used in five cases, was complementary. Most of our cases (9) had complete restoration of the thrombosed subcutaneous breast vein, either spontaneously (4), or after anti-inflammatory medication (5). Only one of our patients had surgical management (vein excision) due to delayed remission. None of our cases was related to breast cancer.     

Do racial differences exist in the association between pregnancy-induced hypertension and breast cancer risk?

Background: Previous studies investigating the relationship between pregnancy-induced hypertension (PIH) and breast cancer risk have yielded inconsistent results. Unlike numerous Western studies, studies have reported that PIH may be a risk factor for breast cancer in Western Asian women. To confirm these results, we designed a retrospective population-based cohort study to assess the relationship between PIH and subsequent risk for breast cancer in Taiwan. Methods: Patients with newly diagnosed PIH were selected from the Taiwan National Health Insurance Research Database (NHIRD), and a 1:4 matched cohort of women without PIH based on age and the year of delivery was randomly selected from the same database as the comparison group. The incidence of new-onset breast cancer was assessed in both cohorts. Results: Among the 23.3 million individuals registered in the NHIRD, 26,638 patients with PIH and 106,552 matched controls were identified. The incidence rate of breast cancer was higher in patients with PIH than in the matched controls (incidence rate ratio = 1.09, 95% confidence interval [CI] = 1.09–1.10, p < 0.0001). However, the Kaplan–Meier analysis revealed a similar cumulative incidence rate of breast cancer between the PIH and comparison cohorts (log-rank p = 0.4303). Moreover, results from a multivariate analysis indicated that PIH was not a statistically significant independent risk factor for breast cancer (adjusted hazard ratio = 1.10, 95% CI = 0.87–1.39, p = 0.4247). Conclusions: The present study demonstrated no significant temporal relationship between PIH and risk for subsequent breast cancer in Eastern Asian women.     

Environmental endocrine disruptors and breast cancer: new risk factors?

Human epidemiological studies and experimental animal data strongly suggest that xenobiotics with estrogenic activity may participate in to the increasing incidence of breast cancer, the most frequent cancer all around the world. Several reports have since 15 years reported positive correlations between blood or peritumoral adipose tissue levels of persistent organic compounds including organochloride pesticides and breast cancer risk. Moreover, fetal or perinatal exposition to low doses of such endocrine disruptors induce premalignant or malignant transformation of adult mammary gland in rodents. However, this environmental endocrine disrupter hypothesis still needs to be demonstrated. Further human studies are needed which will consider the exposition window, the association of several xenoestrogens, the molecular mechanisms involved and the possible individual genetic susceptibility in order to identify pertinent biomarkers and to define acceptable environmental concentration levels for agricultural or industrial chemical new products to be used.     

Is low-grade serous ovarian cancer part of the tumor spectrum of hereditary breast and ovarian cancer?

Objective

To determine whether women with low-grade serous ovarian cancer (LGSOC) have personal and family histories of breast and ovarian cancer that are less suggestive of Hereditary Breast and Ovarian Cancer (HBOC), as compared to women with high-grade serous ovarian cancer (HGSOC).

Methods

A single institution, case-control retrospective review of medical records was conducted. Personal demographics, personal cancer history, and family history of breast and ovarian cancer of women with LGSOC were collected and compared to controls with HGSOC, which is known to be associated with HBOC.

Results

195 cases of LGSOC and 386 controls with HGSOC were included in the analysis. Women with LGSOC were significantly less likely to have a first- or second-degree relative with breast or ovarian cancer (p = 0.0016). Additionally, when the personal and family histories were quantified using the AMyriad BRC mutation prevalence tables, women with LGSOC had lower scores indicative of a less suggestive family history for HBOC (p = 0.027).

Conclusions

In this study, women with LGSOC had family histories that were less suggestive of HBOC compared to women with HGSOC, especially when the degree of relatedness of affected relatives was taken into account. By beginning to determine if LGSOC is part of the tumor spectrum seen in HBOC, this study is an important step towards refining hereditary cancer risk assessment for women with ovarian cancer.     

What are the real risks for breast cancer?

There is a steady drumbeat of peer-reviewed medical articles relating risks of breast cancer from a variety of factors. Whether or not the reported factors are under the control of any given individual, they have been trumpeted by the lay media and are responsible for the understandable finding among women that breast cancer generates more anxiety than heart disease, even though the number of US women who died of heart disease in 2010 is over seven and a half times the number who fell victim to breast cancer. This article attempts to reduce the anxiety-inducing barrage of these reports by orienting physicians to better understand the validity of reported breast cancer risk factors. We hope to provide this understanding by: explaining the difference between relative and absolute risk, encouraging application of the 95% confidence interval to better evaluate the statistical validity of any given risk factor; placing the reported risk factors in the context of an accepted risk factor like cigarette smoking and lung cancer; and communicating the limits of statistical validity in the absence of reproducibility. This review will, to a small degree, provide a balance to the reports currently dominating the literature.     

How to avoid the uncertainties of intraoperative examination of the sentinel lymph node in breast cancer?

Numerous researchers have confirmed the diagnostic relevance of the sentinel lymph node (SLN) examination in breast carcinoma. Many technical problems are analyzed which are correlated with the intraoperative examination of the SLN and its sensitivity and specificity. In order to avoid the incidence of false positive or false negative intraoperative diagnoses, the authors propose the examination of SLN under local anesthesia, awaiting its definitive analysis before carrying out tumorectomy and/or axillary lymphadenectomy.     

How to avoid the uncertainties of intraoperative examination of the sentinel lymph node in breast cancer?

The sentinel lymph node procedure is now admitted by many teams for axillary evaluation in the early stage of breast cancer. The classical technique consists in an intraoperative examination of the sentinel lymph node under general anaesthesia during tumorectomy, deciding whether or not complete axillary lymphadenectomy must be done. Intraoperative examination seems to us to have a poor predictive value. In the case of a false positive, the surgeon would perform lymphadenectomy unnecessarily, while a false negative would mean that the patient would have to be re-operated for lymphadenectomy once the definitive results have become available. For all these reasons, we propose the detection of the sentinel lymph node under local anaesthesia and to await its definitive analysis before carrying out tumorectomy on the patient and axillary lymphadenectomy if necessary under general anesthesia. Hence, we consider that the best way to avoid the uncertainties of an intraoperative examination of the sentinel lymph node is not to carry out intraoperative examinations.     

Genetic polymorphism of estrogen receptor alpha--a risk factor of osteoporosis?

Considering the prolonged population lifetime, there is an increasing number of elderly people suffering from osteoporosis. At present the prevention of osteoporosis is one of the most important problems in medicine. The development of genetic investigations and molecular biology gives new possibilities for discovering risk factors and early prevention of this condition. This is a brief summary referring the polymorphisms of estrogen receptors and their significance in the pathogenesis and prevention of osteoporosis.