High Risk Of Breast Cancer

Ductal hyperplasia refers to a proliferative condition in which there is increased cellularity of the lining epithelium. It is classified into usual (regular or ordinary) hyperplasia and atypical hyperplasia. The diagnosis is made on breast biopsy.

Atypical lobular hyperplasia is characterized by abnormal cells within one or more of the breast lobules.

Both atypical ductal and atypical lobular hyperplasia are associated with an increased risk of breast cancer. The Gail model incorporates the presence of atypia into risk assessment http://www.cancer.gov/bcrisktool/

If the 5 year risk of breast cancer calculated by this model is 1.67% or more, then chemporeventive drugs such as tamoxifen, raloxifene or exemestane may be offered to reduce risk.

Patients with atypia found on a core needle biopsy should undergo excisional biopsy of the surrounding tissue to exclude a nearby cancer. Ductal hyperplasia refers to a proliferative condition in which there is increased cellularity of the lining epithelium. It is classified into usual (regular or ordinary) hyperplasia and atypical hyperplasia. The diagnosis is made on breast biopsy.

Atypical lobular hyperplasia is characterized by abnormal cells within one or more of the breast lobules.

Both atypical ductal and atypical lobular hyperplasia are associated with an increased risk of breast cancer. The Gail model incorporates the presence of atypia into risk assessment http://www.cancer.gov/bcrisktool/

If the 5 year risk of breast cancer calculated by this model is 1.67% or more, then chemporeventive drugs such as tamoxifen, raloxifene or exemestane may be offered to reduce risk.

Patients with atypia found on a core needle biopsy should undergo excisional biopsy of the surrounding tissue to exclude a nearby cancer.

Risk stratification based upon family history and established risk factors is essential. There are models such as the GAIL model which can calculate risk based upon age, age of menarche, age first live birth, # first degree relatives with breast cancer, hx breast biopsies and finding of atypia. For patients determined to be at high risk, genetic counseling to discuss possible benefit of BRCA testing is important. Surveillance may include self, exam, clinical breast exam, mammography, ultrasound and MRI depending on the level of risk. Risk stratification based upon family history and established risk factors is essential. There are models such as the GAIL model which can calculate risk based upon age, age of menarche, age first live birth, # first degree relatives with breast cancer, hx breast biopsies and finding of atypia. For patients determined to be at high risk, genetic counseling to discuss possible benefit of BRCA testing is important. Surveillance may include self, exam, clinical breast exam, mammography, ultrasound and MRI depending on the level of risk.

Thanks for this repsonse as well...again- not sure why this is not more widely known to the public...It is my understanding that you do not even have to take that many doses before one can be negatively effected...as data has also shown that for those people with mild depression, there is no benefit in taking the said antidepressants, this would seem especially wrong for psychiatrists and others to be promoting these drugs...This seems a bit scary to me, and patients taking these drugs seem to be treated as guinea pigs...shouldn't these studies be done PRIOR to people being allowed to take them?! Thanks again for your great responses. Rachel Your question relates to the paper by L Cosgrove and others published in April 2011, Antidepressants and breast and ovarian cancer risk: a review of the literature and researchers' financial associations with industry, PLoS One. 2011 Apr 6;6(4). It has been purported that antidepressants (ADs) may increase risk of breast and ovarian cancer, however results are mixed. The authors reviewed 61 articles published in English that assessed the relationship between AD use and cancer risk. Forty-one of those papers concluded no association, whereas 20 found a positive association. There was more likely to be a negative association if the investigators had financial ties with industry. Overall, the pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11, meaning there was a 1.11 fold greater chance of breast/ovarian cancer with AD use. They conclude that these findings warrant further study. They do not conclude that women taking ADs should be labeled as high-risk.
Comments on this article can be found on the Alliance for Human Research Protection website http://www.ahrp.org/cms/content/view/795/9/. Cosgrove is quoted as saying, “I would want to consider nondrug treatment if I was mildly depressed, given our data.”

It's important to differentiate between "risk factors" and "high-risk." For example, alcohol intake and increased BMI are both risk factors for breast cancer, however we do not automatically regard women who drink alcohol or are overweight/obese as being "high risk." They should be counseled re. lifestyle changes to reduce risk, not necessarily offered chemoprevention or annual MRIs.
There is a nice review of modifiable and non-modifiable risk factors on the American Cancer Society website at http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-risk-factors.
It is recognized that rates of breast cancer vary around the USA, and of course, around the world. The CDC maps out the rates of breast cancer around the USA at http://www.cdc.gov/cancer/breast/statistics/state.htm. Based on 2007 data, the states with the highest incidence of breast cancer are Connecticut, Delaware, District of Columbia, Maine, Massachusetts, Minnesota, New Hampshire, New Jersey, Oklahoma, Oregon, Rhode Island, and Vermont. The states with the highest death rates from breast cancer are Alaska, Arkansas, Delaware, District of Columbia, Illinois, Kentucky, Maryland, New Jersey, North Carolina, Ohio, Oklahoma, Vermont, and Virginia.
There is an interesting report by C A Clarke and others looking at variations of breast cancer rates in California: Population attributable risk of breast cancer in white women associated with immediately modifiable risk factors BMC Cancer 2006, 6:170. They conclude that variations may be attributable to lifestyle and state "the relatively feasible lifestyle changes of discontinuing estrogen/progestin replacement therapy use, reducing alcohol consumption, increasing physical activity, and lengthening breastfeeding duration could lower population breast cancer incidence substantially." It's important to differentiate between "risk factors" and "high-risk." For example, alcohol intake and increased BMI are both risk factors for breast cancer, however we do not automatically regard women who drink alcohol or are overweight/obese as being "high risk." They should be counseled re. lifestyle changes to reduce risk, not necessarily offered chemoprevention or annual MRIs.
There is a nice review of modifiable and non-modifiable risk factors on the American Cancer Society website at http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-risk-factors.
It is recognized that rates of breast cancer vary around the USA, and of course, around the world. The CDC maps out the rates of breast cancer around the USA at http://www.cdc.gov/cancer/breast/statistics/state.htm. Based on 2007 data, the states with the highest incidence of breast cancer are Connecticut, Delaware, District of Columbia, Maine, Massachusetts, Minnesota, New Hampshire, New Jersey, Oklahoma, Oregon, Rhode Island, and Vermont. The states with the highest death rates from breast cancer are Alaska, Arkansas, Delaware, District of Columbia, Illinois, Kentucky, Maryland, New Jersey, North Carolina, Ohio, Oklahoma, Vermont, and Virginia.
There is an interesting report by C A Clarke and others looking at variations of breast cancer rates in California: Population attributable risk of breast cancer in white women associated with immediately modifiable risk factors BMC Cancer 2006, 6:170. They conclude that variations may be attributable to lifestyle and state "the relatively feasible lifestyle changes of discontinuing estrogen/progestin replacement therapy use, reducing alcohol consumption, increasing physical activity, and lengthening breastfeeding duration could lower population breast cancer incidence substantially."

It is well known that high doses of ionizing radiation increase risk for breast cancer. Examples are exposure to the atomic bomb explosions in Japan (particularly if exposure occurred before age 30), and therapeutic radiation to the chest area, such as for Hodgkin's lymphoma. E M John and others report an increased risk of 3.55 fold following previous therapeutic radiation. Risk conferred by diagnostic x rays to the spine is harder to quantify. A study from the Breast Cancer Family Registry Int J Cancer. 2007 Jul 15;121(2):386-94 found that diagnostic chest x rays for TB or pneumonia increased breast cancer risk 2 fold. Chest x rays for other conditions, spine x rays, and cardiac catheterization did not increase breast cancer risk.
There are several reports regarding risk associated with x rays for scoliosis specifically. D A Hoffman and others studied 1,030 women with scoliosis who were seen at four Minneapolis area medical facilities between 1935 and 1965 J Natl Cancer Inst 81:1307–1312, 1989. 11 cases of breast cancer were reported, compared with six expected. Their conclusion was that frequent exposure to low-level diagnostic radiation during childhood or adolescence may increase the risk of breast cancer.
C M Ronckers and others performed a retrospective analysis of 3,010 women, diagnosed with spinal curvature between 1912 and 1965 in 14 U.S. pediatric orthopedic centers Cancer Epidemiol Biomarkers Prev 2008;17(3):605–13. They reported 78 cases of breast cancer after 118,905 woman-years of follow-up, median follow-up 35.5 years. They concluded that women with abnormal spinal curvature who were exposed to diagnostic x rays during childhood and adolescence were at increased risk of breast cancer, with a borderline statistically significant radiation dose-response relationship. Patients who reported having female blood relatives with breast cancer appeared to be at higher risk of radiation-related breast cancer than those who did not report such family history. Regarding what to do about these findings the authors state, "for women exposed to multiple x rays in the past, compliance with current breast cancer screening guidelines is warranted. Health-care practitioners should be aware that women with a history of scoliosis may be at increased risk of breast cancer". It is well known that high doses of ionizing radiation increase risk for breast cancer. Examples are exposure to the atomic bomb explosions in Japan (particularly if exposure occurred before age 30), and therapeutic radiation to the chest area, such as for Hodgkin's lymphoma. E M John and others report an increased risk of 3.55 fold following previous therapeutic radiation. Risk conferred by diagnostic x rays to the spine is harder to quantify. A study from the Breast Cancer Family Registry Int J Cancer. 2007 Jul 15;121(2):386-94 found that diagnostic chest x rays for TB or pneumonia increased breast cancer risk 2 fold. Chest x rays for other conditions, spine x rays, and cardiac catheterization did not increase breast cancer risk.
There are several reports regarding risk associated with x rays for scoliosis specifically. D A Hoffman and others studied 1,030 women with scoliosis who were seen at four Minneapolis area medical facilities between 1935 and 1965 J Natl Cancer Inst 81:1307–1312, 1989. 11 cases of breast cancer were reported, compared with six expected. Their conclusion was that frequent exposure to low-level diagnostic radiation during childhood or adolescence may increase the risk of breast cancer.
C M Ronckers and others performed a retrospective analysis of 3,010 women, diagnosed with spinal curvature between 1912 and 1965 in 14 U.S. pediatric orthopedic centers Cancer Epidemiol Biomarkers Prev 2008;17(3):605–13. They reported 78 cases of breast cancer after 118,905 woman-years of follow-up, median follow-up 35.5 years. They concluded that women with abnormal spinal curvature who were exposed to diagnostic x rays during childhood and adolescence were at increased risk of breast cancer, with a borderline statistically significant radiation dose-response relationship. Patients who reported having female blood relatives with breast cancer appeared to be at higher risk of radiation-related breast cancer than those who did not report such family history. Regarding what to do about these findings the authors state, "for women exposed to multiple x rays in the past, compliance with current breast cancer screening guidelines is warranted. Health-care practitioners should be aware that women with a history of scoliosis may be at increased risk of breast cancer".

A number of factors contribute to risk of breast cancer. The Gail model was used by the NSABP in the chemoprevention trials P-01 (tamoxifen versus placebo) P-02 (STAR, tamoxifen versus raloxifene). High risk was defined as a five year risk of 1.67% or greater. The modified Gail model is available online http://www.cancer.gov/bcrisktool/. It takes into account current age, ethnic origin, age at first menstrual period, age at first live birth, family history of breast cancer (first degree relatives), number of surgical excisional biopsies and whether or not atypical hyperplasia was found on those biopsies. Harvard School of Public Health developed the Harvard Cancer Risk Index. In 2007 this online risk assessment tool moved to Washington University in St. Louis and can be accessed at http://www.yourdiseaserisk.wustl.edu. The Tyrer-Cusick, BRCAPRO and BOADICEA models are also used to determine likelihood of carrying a BRCA mutation. A number of factors contribute to risk of breast cancer. The Gail model was used by the NSABP in the chemoprevention trials P-01 (tamoxifen versus placebo) P-02 (STAR, tamoxifen versus raloxifene). High risk was defined as a five year risk of 1.67% or greater. The modified Gail model is available online http://www.cancer.gov/bcrisktool/. It takes into account current age, ethnic origin, age at first menstrual period, age at first live birth, family history of breast cancer (first degree relatives), number of surgical excisional biopsies and whether or not atypical hyperplasia was found on those biopsies. Harvard School of Public Health developed the Harvard Cancer Risk Index. In 2007 this online risk assessment tool moved to Washington University in St. Louis and can be accessed at http://www.yourdiseaserisk.wustl.edu. The Tyrer-Cusick, BRCAPRO and BOADICEA models are also used to determine likelihood of carrying a BRCA mutation.

I use the definition used in the NSABP chemoprevention trials NSABP-P01 and -P02. In those studies the Gail model was used and high risk was defined as a five year risk of 1.67 or greater. This number is the cut-off for referral for consideration for tamoxifen or raloxifene to decrease risk. The Gail model takes into account current age, ethnicity, age of first menstrual period, age of first live birth, family history of breast cancer (first degree relatives), number of excisional biopsies and whether or not atypia was found on those biopsies. Other models exist such as BRCAPRO, Claus, or Tyrer-Cuzick. The American Cancer Society recommends annual MRI for patients who have a lifetime risk of breast cancer of 20% or higher.

I am a pragmatist by nature, and I know that when I am on the phone with an insurance company to obtain pre-certification for a screening breast MRI for one of my patients, I will be asked the Gail model lifetime risk. Therefore this is the model I use most often, the calculator for which I carry in my pocket.

The model can underestimate risk when there is inherited predisposition, such as BRCA 1 or 2 positivity. As I'm sure many of the readers of this website know, female carriers of a deleterious mutation of BRCA 1 or 2 have a lifetime risk of breast cancer of 50-80%. I use the definition used in the NSABP chemoprevention trials NSABP-P01 and -P02. In those studies the Gail model was used and high risk was defined as a five year risk of 1.67 or greater. This number is the cut-off for referral for consideration for tamoxifen or raloxifene to decrease risk. The Gail model takes into account current age, ethnicity, age of first menstrual period, age of first live birth, family history of breast cancer (first degree relatives), number of excisional biopsies and whether or not atypia was found on those biopsies. Other models exist such as BRCAPRO, Claus, or Tyrer-Cuzick. The American Cancer Society recommends annual MRI for patients who have a lifetime risk of breast cancer of 20% or higher.

I am a pragmatist by nature, and I know that when I am on the phone with an insurance company to obtain pre-certification for a screening breast MRI for one of my patients, I will be asked the Gail model lifetime risk. Therefore this is the model I use most often, the calculator for which I carry in my pocket.

The model can underestimate risk when there is inherited predisposition, such as BRCA 1 or 2 positivity. As I'm sure many of the readers of this website know, female carriers of a deleterious mutation of BRCA 1 or 2 have a lifetime risk of breast cancer of 50-80%.

Some of the risk factors that are used to determine if someone is at high risk for breast cancer are:
- if a woman had breast cancer in one breast, there is an increased risk of developing cancer in the other breast unrelated to the first cancer.
- direct family history increases the risk of breast cancer, especially if the family history is a first degree relative.
- having two first-degree relatives who had breast cancer further increases risk
- generationally if the cancer in the family was in both breasts
- if a breast biopsy revealed atypical hyperplasia (lobular or ductal)
- if the woman tested positive for BRCA -1 or BRCA-2 positive
- if the woman's relatives tested BRCA positive
- if your ancestry is Eastern and Central European (Ashkenazi) Jewish
- if ovarian cancer has been in the family
- if a male relative has had breast cancer
- if the person experienced chest radiation between the ages of 10-30 The National Cancer Institute has a tool on their website, The Gail Model, that helps women over 35 determine their risk for invasive breast cancer. It can be accessed through this link http://www.cancer.gov/bcrisktool/