Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.
"Antihormone therapies can also be used to reduce the risk of developing breast cancer. Women at high risk for the disease are usually treated with Tamoxifen and another selective estrogen receptor modulator, raloxifene, and several other aromatase inhibitors . "
[Show abstract][Hide abstract] ABSTRACT: Breast cancer is the most common malignancy and the leading cause of cancer deaths in women worldwide. While specific genetic mutations have been linked to 5-10% of breast cancer cases, other environmental and epigenetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive breast cancer molecular profile is needed to develop more effective target therapies. Until recently, identifying genetic cancer mutations via personalized DNA sequencing was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 105 human breast cancer samples. The sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.
PLoS ONE 06/2014; 9(6):e99306. DOI:10.1371/journal.pone.0099306 · 3.23 Impact Factor
"Two of these studies compared raloxifene against placebo and one against tamoxifen. The original Multiple Outcomes of Raloxifene Evaluation (MORE) study was conducted to study the impact of raloxifene on osteopenia, however, a secondary trial (Continued Outcomes of Raloxifene Evaluation—CORE study) computed breast cancer incidence during extended follow up . Similarly the Raloxifene Use for The Heart (RUTH) trial investigated reduction in breast cancer and cardiovascular events among women with cardiac risk factors . "
[Show abstract][Hide abstract] ABSTRACT: Women who are at high risk of breast cancer can be offered chemoprevention. Chemoprevention strategies have expanded over the past decade and include selective receptor modulator inhibitors and aromatase inhibitors. Physicians are expected to provide individualized risk assessments to identify high risk women who may be eligible for chemoprevention. It is prudent that physicians utilize a shared decision approach when counseling high risk women about their preventive options. Barriers and misperceptions however exist with patient and physician acceptance of chemoprevention and continue to impede uptake of chemoprevention as a strategy to reduce breast cancer risk. Programs to increase awareness and elucidate the barriers are critical for women to engage in cancer prevention and promote chemoprevention adherence.
"In addition to tamoxifen, other SERMs such as raloxifene and lasofoxifene are also used as chemoprevention agents. The STAR trial, MORE trial, and CORE trial have studied the role of raloxifene for prevention of breast cancer and have shown positive results . However, a recent study by Viring and colleagues  reported that while raloxifene reduced the risk of invasive breast cancer, it was not associated with decreased incidence of DCIS. "
[Show abstract][Hide abstract] ABSTRACT: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous neoplasm with invasive potential. Risk factors include age, family history, hormone replacement therapy, genetic mutation, and patient lifestyle. The incidence of DCIS has increased due to more widespread use of screening and diagnostic mammography; almost 80% of cases are diagnosed with imaging with final diagnosis established by biopsy and histological examination. There are various classification systems used for DCIS, the most recent of which is based on the presence of intraepithelial neoplasia of the ductal epithelium (DIN). A number of molecular assays are now available that can identify high-risk patients as well as help establish the prognosis of patients with diagnosed DCIS. Current surgical treatment options include total mastectomy, simple lumpectomy in very low-risk patients, and lumpectomy with radiation. Adjuvant therapy is tailored based on the molecular profile of the neoplasm and can include aromatase inhibitors, anti-estrogen, anti-progesterone (or a combination of antiestrogen and antiprogesterone), and HER2 neu suppression therapy. Chemopreventive therapies are under investigation for DCIS, as are various molecular-targeted drugs. It is anticipated that new biologic agents, when combined with hormonal agents such as SERMs and aromatase inhibitors, may one day prevent all forms of breast cancer.
International Journal of Surgical Oncology 09/2012; 2012:761364. DOI:10.1155/2012/761364
Ravichandra Juluri, Evuru Prashanth, D Gopalakrishnan, Rahul Kathariya, Archana Devanoorkar, Vidya Viswanathan, Georgios E Romanos
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