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Family breast cancer raises risk

Monday 19 January 2009

Women with a family history of breast cancer are four times more likely to develop the disease, even if they don’t have high-risk genes, The Times reported. It said that researchers say that having a family history of the disease could be enough for doctors to offer preventive treatments. The Daily Express gave the story the headline “Rogue gene that can lead to breast cancer”, and said that “scientists have pinpointed the women who are most at risk”.

This study looked at the risk of breast cancer in women with a family history of the disease, but without the ‘high-risk’ BRCA1 or BRCA2 mutations. It is already known that these women have a raised risk, and this study estimated how much it increased. The study was well conducted, but has some shortcomings, including the fact that the women self-reported their breast cancer diagnoses.

Despite the Daily Express headline, no rogue gene was identified, and saying that the women most at risk have been ‘pinpointed’ is overstating the finding. As commentators have said, this study can be used to “strengthen advice to women with a strong family history of breast cancer but no evidence of a gene mutation” (Dr Lesley Walker, as quoted in the Express ).

Where did the story come from?

Drs K. A. Metcalfe and colleagues from the University of Toronto, the Women’s College Research Institute in Toronto, and the BC Cancer Agency in Vancouver carried out this study. The work was funded by the Canadian Breast Cancer Foundation. The study was published in the peer-reviewed medical journal British Journal of Cancer .

What kind of scientific study was this?

Mutations in the BRCA1 and BRCA2 genes increase a woman’s chance of getting breast cancer during her lifetime. For women with a strong family history of breast cancer, genetic testing is offered to determine whether she is a carrier of one of these mutations. Women who are found to be carriers will then be monitored more closely for breast cancer, or may opt to have both breasts removed as a prophylactic (preventative) measure. However, there are some women who have strong family histories of breast cancer but who do not have the mutations in the BRCA1 and BRCA2 genes. The researchers say that although these women are thought to have a higher risk of breast cancer, it is unclear to what extent. This study aimed to estimate that risk.

Subjects were obtained from a database of families that had been tested and found not to have the BRCA1 and BRCA2 mutations. The families all had a strong history of breast cancer, and included at least one woman who was affected by breast cancer and had tested negative for the mutations. Testing took place at a Canadian centre between 1993 and 2003. To be eligible for inclusion, the family had to have two or more women who had breast cancer diagnosed under 50 years of age, or three or more women with breast cancer diagnosed at any age.

The researchers contacted the women with breast cancer who had first been tested for the BRCA mutations (called the proband). Each proband was interviewed and asked about all female first-degree relatives of breast cancer cases within the family, including their age, cancer status and prophylactic treatment. First-degree relatives had to be over 18 and free of breast cancer at the time that the proband was tested. In this way, the researchers were able to identify all first-degree relatives of women who were affected with breast cancer.

Women were followed-up for an average of six years from the time of the genetic testing of the proband. The researchers estimated the lifetime risk of breast cancer in these women, stratified by five-year ages, and compared this lifetime risk with that expected for all Canadian women of these ages.

What were the results of the study?

In the 474 families included in this study, there were 874 women with breast cancer. From the cancer-free, first-degree relatives of these women, 1,492 were eligible for analysis. During the follow-up time, the researchers expected 15 women to develop breast cancer (based on Canadian averages) but found that 65 women developed breast cancer, equivalent to about a four-fold increase. For this whole cohort, this amounted to a 40% risk over the woman’s lifetime. There was no increase in risk of ovarian or colon cancers among these women.

What interpretations did the researchers draw from these results?

The researchers conclude that women from high-risk breast cancer families in which a BRCA1 or BRCA2 mutation cannot be found are at increased risk of breast cancer. As such, they need to be counselled about this and about their options. They say that although the increase in risk is not as high as in women who carry BRCA mutations, it is still significantly higher than in the general population.

What does the NHS Knowledge Service make of this study?

BRCA mutations have been linked to an increased risk of breast cancer in women. Women with a family history of breast cancer are usually tested for these mutations and, if found to have them, are offered prophylactic treatment. In this study, researchers have shown that women with a familial history of breast cancer are at increased risk even if they do not have BRCA1 or BRCA2 mutations (which are known to increase risk substantially). There is an ongoing discussion about what prophylactic treatments to offer women in this situation, but the researchers suggest that such women may qualify for MRI screening or prophylactic tamoxifen treatment.

The researchers have highlighted the following shortcomings in their study:

  • They say that all cancers that they documented were self-reported (unconfirmed by pathology).
  • Not everyone with breast cancer had a genetic test, i.e. the researchers assumed the BRCA status for a family based on the test result from one unaffected female member. They say it is possible that this person may have been a sporadic case of mutation (not representative of the rest of her family).
  • Also, it may not be possible to apply the results to families outside of Canada. The factors (genetic or environmental) that may be contributing to an increased risk of breast cancer in this group are likely to differ across populations.

This is an important area of research, and the discussion has implications for the way high-risk women are managed.

Sir Muir Gray adds...

This is important research. What you get from your parents is not only your genes - it is also your lifestyle, such as your dietary and exercise habits.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Family link raises breast cancer risk, study shows. The Guardian

, January 19 2009

Rogue gene that can lead to breast cancer

Daily Express, 19 January 2009

Breast cancer risk rises four-fold among families.

Metro, 19 January 2009

Links to the science

Lostumbo L, Carbine NE, Wallace J, Ezzo J, Dickersin K.

Prophylactic mastectomy for the prevention of breast cancer.

Cochrane Database of Systematic Reviews 2004, Issue 4

Sivell S, Iredale R, Gray J, Coles B.

Cancer genetic risk assessment for individuals at risk of familial breast cancer.

Cochrane Database of Systematic Reviews 2007, Issue 2

Metcalfe KA, Finch A, Poll A, et al.

Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation.

British Journal of Cancer 2008; online publication 16 December