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
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.
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.
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.