Identification of signaling pathways in early mammary gland development by mouse genetics

The mammary gland develops as an appendage of the ectoderm. The prenatal stage of mammary development is hormone independent and is regulated by sequential and reciprocal signaling between the epithelium and the mesenchyme. A number of recent studies using human and mouse genetics, in particular targeted gene deletion and transgenic expression, have identified some of the signals that control specific steps in development. This process involves cell specification and proliferation, reciprocal tissue interactions and cell migration. Since some of these events are recapitulated during tumorigenesis, an understanding of these signaling pathways may contribute to the development of targeted therapies and novel drugs

A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

ABSTRACT: BACKGROUND: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting. METHODS: An unselected sample of 1,987 women with and without breast cancer was studied with regard to the age of diagnosis of breast cancer. RESULTS: The risk of early-onset breast cancer was increased when there were: (1) at least 2 cases of female breast cancer in first-degree relatives (yes/no; HR at age 30: 3.09; 95% CI: 128-7.44), (2) at least 2 cases of female breast cancer in first or second-degree relatives under the age of 50 (yes/no; HR at age 30: 3.36; 95% CI: 1.12-10.08), (3) at least 1 case of female breast cancer under the age of 40 in a first- or second-degree relative (yes/no; HR at age 30: 2.06; 95% CI: 0.83-5.12) and (4) any case of bilateral breast cancer (yes/no; HR at age 30: 3.47; 95%: 1.33-9.05). The positive predictive value of having 2 or more of these characteristics was 13% for breast cancer before the age of 70, 11% for breast cancer before the age of 50, and 1% for breast cancer before the age of 30. CONCLUSION: Applying family history related criteria in an unselected population could result in the screening of many women who will not develop breast cancer at an early age

Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer.

Breast cancer is a common cancer that occurs due to different epigenetic alterations and genetic mutations. Various epidemiological studies have demonstrated an inverse correlation between breast cancer incidence and flavonoid intake. The anti-cancer action of flavonoids, a class of polyphenolic compounds that are present in plants, as secondary metabolites has been a major topic of research for many years. Our review analysis demonstrates that flavonoids exhibit anti-cancer activity against breast cancer occurring in different ethnic populations. Breast cancer subtype and menopausal status are the key factors in inducing the flavonoid\u27s anti-cancer action in breast cancer. The dose is another key factor, with research showing that approximately 10 mg/day of isoflavones is required to inhibit breast cancer occurrence. In addition, flavonoids also influence the epigenetic machinery in breast cancer, with research demonstrating that epigallocatechin, genistein, and resveratrol all inhibited DNA methyltransferase and altered chromatin modification in breast cancer. These flavonoids can induce the expression of different tumor suppressor genes that may contribute to decreasing breast cancer progression and metastasis. Additional studies are required to confirm the contribution of epigenetic modifications by flavonoids to breast cancer prevention

Overdiagnosis and overtreatment of breast cancer: Overdiagnosis in randomised controlled trials of breast cancer screening

Data from randomised controlled trials of mammographic screening can be used to determine the extent of any overdiagnosis, as soon as either a time equivalent to the lead-time has elapsed after the final screen, or the control arm has been offered screening. This paper reviews those randomised trials for which breast cancer incidence data are available. In recent trials in which the control group has not been offered screening, an excess incidence of breast cancer remains after many years of follow-up. In those trials in which the control arm has been offered screening, although there is a possible shift from invasive to in situ disease, there is no evidence of overdiagnosis as a result of incident screens

Exploring factors contributing to low uptake of the NHS Breast Cancer Screening Programme among Black African women in the UK

Breast cancer is the most common cancer among women in the United Kingdom (UK) accounting for about 15% of cancer deaths. The National Breast Cancer Screening Programme in the UK was introduced in 1988 to assist with early detection and better management of breast cancer. Black and Minority Ethnic (BME) women however have a low uptake of the National Breast Screening programme when compared to their White counterparts. Within the BME group, Black African women have the lowest uptake of screening services and are more likely to have an advanced stage of the disease at diagnosis, leading to poorer survival rates than White women. This study aimed to explore the factors that lead to low uptake of the National Breast Cancer Screening Programme  among Black African women living in Luton and present action points to local breast cancer services. Using a qualitative research design, six focus groups were conducted with a total of twenty-five Black African women residing in Luton between May and June in 2013. Data was analysed thematically using the framework approach. Four main themes emerged across the focus group discussions: knowledge and beliefs about breast cancer and risk factors, prevention of breast cancer and awareness of the NHS breast screening service, delays in attending the NHS breast screening service and suggestions for improving information on breast cancer and the NHS breast cancer screening service. The findings from this study suggest the need for more targeted information on breast cancer and screening services for Black African women. This could help improve the uptake of the NHS breast screening service, promote early help-seeking behaviour and improve breast cancer outcomes for this ethnic group.

Advances in Preventive Therapy for Estrogen-Receptor-Negative Breast Cancer.

Preventing breast cancer is an effective strategy for reducing breast cancer deaths. The purpose of chemoprevention (also termed preventive therapy) is to reduce cancer incidence by use of natural, synthetic, or biological agents. The efficacy of tamoxifen, raloxifene, and exemestane as preventive therapy against estrogen-receptor (ER)-positive breast cancer is well established for women at increased risk for breast cancer. However, because breast cancer is a heterogeneous disease, distinct preventive approaches may be required for effective prevention of each subtype. Current research is, therefore, focused on identifying alternative mechanisms by which biologically active compounds can reduce the risk of all breast cancer subtypes including ER-negative breast cancer. Promising agents are currently being developed for prevention of HER2-positive and triple-negative breast cancer (TNBC) and include inhibitors of the ErbB family receptors, COX-2 inhibitors, metformin, retinoids, statins, poly(ADP-ribose) polymerase inhibitors, and natural compounds. This review focuses on recent progress in research to develop more effective preventive agents, in particular for prevention of ER-negative breast cancer

Breast tumor diagnosis in digital mammograms

Breast cancer has been classified as the most common cancer in most part of the world [1]. Breast cancer is caused by the growth of the abnormal cells in the breast. Breast cancer not only develops in women but also on men. However, the incidents of breast cancer in women are more common than men. Breast cancer is dangerous and may take away one’s life if there is no early detection and treatment are not done to remove the cancer cell present in the breast. Although the prevention methods for breast cancer may be unclear, it is found out that the earlier the detection and treatment conducted to the patients, the higher the survivability of the patients. Digital mammography is a specific type of breast imaging that uses low-dose x-rays to detect cancer early especially before women experience any symptoms [2]. The early signs of breast cancer can be detected in mammograms. Hence, digital mammograms have been classified as one of the best methods to detect breast cancer. In the studies [2] has shown that digital mammograms produce a better result than film mammograms in a group of young women, premenopausal and perimenopausal women, and women with dense breasts. 335 women were found to be infected with breast cancer in the test. However, there is also a limitation present in digital mammograms. High breast density can affect the performance of diagnosis in digital mammography as it increases the difficulty in finding abnormalities in a mammogram. Digital mammograms are only able to yield the best accuracy in the result for the women who are under the age of 50 and absent from menopause or undergoes menopause in a period of less than one year

Unique Breast Cancer Features Within the Vietnamese Population

BACKGROUND: Breast cancer is known to be a heterogeneous disease across women, and even within individual tumors. However, relatively little is known about heterogeneity across cultures. There has been some evidence to suggest that Asian women are more likely to have HER2+ breast cancer than their Caucasian counterparts. PURPOSE: The aim of this study was to further investigate the unique pattern of breast cancer incidence and subtype in the Vietnamese population. METHODS: We retrospectively collected data on all Vietnamese women diagnosed with invasive breast cancer at the Lester & Sue Smith Breast Center in Houston, Texas over a four year period. We recorded the subtype of breast cancer, tumor grade, age at diagnosis, and menopausal status for each woman. We then compared these characteristics between our population of Vietnamese breast cancer patients, and an ethnically diverse group of American women from the 2010 SEER registry. RESULTS: We discovered that 15 of 33 Vietnamese patients diagnosed in our breast center had HER2 over-expressing breast cancer, resulting in a 45% rate of HER2 positivity. Compared with the 2010 Surveillance, Epidemiology, and End Results (SEER) registry data that encompasses 28% of all US breast cancer patients diagnosed that year, regardless of race, the Smith Clinic Vietnamese cohort had a statistically significant higher rate of HER2+ breast cancer, with an odds ratio of 4.7 (45% vs. 15%, p CONCLUSIONS: Vietnamese breast cancer patients, especially those older than 50 years old, tend to have higher rates of HER2+ breast cancer than the general population. This unique pattern of breast cancer merits further study, as it may reflect a genetic mutation or environmental exposure which is more common among Vietnamese women

Targeted therapy for breast cancer prevention.

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer