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Genetic risk for breast cancer

Having the defect gene which check for abnormal copying of DNA during mitosis (thus greatly accelerating the mutation rate—cancer requires at least 6 specific types of mutation, except blood cancers).  The risk increases from 12% risk of breast cancer by the age of 70 to 85%--and a similar increase for ovarian cancer, from 1-2% to 35-50%.  The therapy for such women is to have a radical hysterectomy (ovary and tubes) and also their breast removed--jk. 


Breast Cancer gene and risk reduction


From Huffington Post by Dr. Rock Positano, Posted December 21, 2007


Breast Cancer Genes:  New Strategies for Protecting Women

Breast Cancer Genes:  New Strategies for Protecting Women

Breast cancer is still very much alive. Over 200,000 women will be diagnosed and 41,000 women are expected to die from breast cancer in the US in 2007. One in eight women will develop breast cancer in their lifetime if they live to 85 years. According to Dr. Michael Osborne, Director of Breast Cancer Programs at Continuum Cancer Center, of New York at Beth Israel Medical Center, an important risk factor for breast cancer is a family history of breast cancer. Genetic testing can help identify individuals who have a highly increased risk of developing cancer before it occurs.

We know that all cancers are genetic but only a few are due to a hereditary predisposition. Hereditary cancer accounts for 7-10% of cancer cases. "For these individuals, they inherited, either from their mother or father, a gene with a mutation. Although an individual with a hereditary cancer predisposition has a high risk of developing breast cancer this does not mean they are at an increased risk for all other cancers," says Dr. Osborne. He further adds that "predisposition increases the risk for certain cancers, depending on which gene has a mutation. It is also important to note that this does not mean that every individual who carries a gene mutation would definitely develop cancer."

Specifically for breast and ovarian cancer, BRCA1 and BRCA2 gene mutations are responsible for the majority of hereditary forms. "Studies indicate that women with a deleterious mutation in the BRCA1 or BRCA2 genes have up to an 85% risk of breast cancer (compared to the general population risk of 12%) and a 27-50% risk of ovarian cancer (compared to the general population risk of ~1-2%), by age 70. In addition, women who have been diagnosed with breast cancer have a 40-60% lifetime risk for a second breast cancer," notes Dr. Osborne. Mutations in these genes may also be associated with other cancers including prostate, male breast cancer, melanoma and pancreatic cancer. Men who carry a BRCA gene mutation have a 7-10% lifetime risk of breast cancer, which is approaching the general population women's risk of breast cancer. According to Karen Ott, genetic counselor at Continuum Cancer Centers at Beth Israel Medical Center, women need extensive discussion about genetic testing before proceeding.

"Women with a high risk for breast cancer, screening recommendations include monthly breast self-exam beginning at age 18 (which applies to all women), semi-annual clinical breast exam starting at age 25 and annual mammogram, ultrasound examination and breast MRI screening starting at age 25," says Dr. Osborne. Some recommend Breast Specific Gamma Imaging using a short lived radioactive isotope. For men, monthly breast self-exam and semi-annual clinical breast exam are recommended. Mammography may also be a consideration.

"Screening tools only detect cancer; early screening does not prevent cancer nor can it guarantee the stage at which a cancer is found," adds Dr. Osborne. He recommends, for women with these higher risks of breast and ovarian cancer, that they consider risk reducing options. "Risk reducing bilateral salpingo-oophorectomy (fallopian tube and ovary removal) which is recommended since the effectiveness of ovarian cancer screening remains unproven, significantly lowers the risk for both ovarian cancer, by up to 97%, and for breast cancer, by approximately 50% (when performed prior to the age of 50)", he comments. The preventive antiestrogen drugs tamoxifen, for premenopausal women, or raloxifene for postmenopausal women. Prophylactic surgery, or so called risk reducing mastectomy results in a significant breast cancer risk reduction of 90-95%.

Dr. Osborne warns that "not all family histories of breast cancer can be accounted for by BRCA1 and BRCA2 gene mutations." There is also a familial cancer risk that accounts for approximately 10-30% of diagnosed cancer cases. In these families we may see close relatives affected with the same type of cancer. The history could be due to chance, shared environments, or genetic factors. The recent discovery of a new group of genes may account for some of these families susceptibility. At this time medical research continues to look for other breast cancer susceptibility genes which will help identify women at a moderate life-time risk for breast cancer.



Dr. Rock, as he is known, is often called on to discuss public health topics featured in his newspaper health column in the New York Post and global issues concerning foot and ankle health.

He is a foot specialist at both the renowned Hospital for Special Surgery in New York City and a member of the Orthopedic Trauma Service at New York-Presbyterian Hospital/Weill Cornell University Medical College where he serves in the capacity as Director of the Foot and Ankle Center. In addition, he serves as the Director of the Non-operative Foot and Ankle Service at the Hospital for Special Surgery and a member of the famed Sports Medicine Service responsible for treating the New York Mets, Giants, Nets, Knicks, PGA , USTA. He is on the professorial staff of Weill Cornell University Medical College/New York-Presbyterian Hospital in New York City.

He earned professional and graduate degrees from Yale University.

Source Conn’s, Current Therapy 2002


Source Conn’s, Current Therapy 2002


The lifetime risk for breast cancer among women is 1 in 8, with a risk of 1 in 54 by the age of 50; 1 in 23 by the age of 60.  Men have a rate of less than 1%.  Other important risk factors include tobacco smoke, large breasts, previous breast cancer, and obesity.


Breast cancers can be broadly divided into noninvasive and invasive.  Noninvasive include ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS).  DCIS is a direct precursor of invasive breast cancer.  DCIS is responsible for 1/3rd of all mammographically detected breast cancers.  The cure rate for DCIS is greater than 98%.  LCIS is a general marker of subsequent breast cancer risk, rather than a direct cancer precursor.  Women with LCIS have approximate a 1% per year risk of developing subsequent invasive breast cancer.  The risk is the same in the biopsied breast as the contra-lateral breast.   


The most common invasive breast cancers are infiltrating ductal carcinoma (75%), and infiltrating lobular carcinoma (10%).  Other less common forms of invasive breast cancer include medullary, tubular, and mucinous. Medullary tends to be slow to metastasize.  Patients with negative axillary lymph nodes at the time of diagnosis have a lifetime recurrence rate of 25-30%.  Node-negative patients with small tumors less than 1 cm in diameter have a recurrence rate of less than 10%.  With fewer than 4 nodes involved the 5-year reoccurrence rate is 40%; more than 4, 75%.  Approximately half of the patients with stage 3 will experience recurrence within 2 years after primary treatment.  Stage 4 (metastatic) breast cancer has a median survival of 2 years. 

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