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Should Breast Cancer Drugs be used Proactively in High-Risk Women?

Posted Jan 18 2013 5:23am

Breast Cancer expert Professor Kefah Mokbel welcomes the recent suggestions from the National Institute of Health and Clinical Excellence (NICE), but urges people to be aware of the latest evidence. He says that there is a need for more trials to prove that that such a chemo-preventative strategy would lead to a significant survival benefit, prior to recommending these treatments.

Expert Comment by Professor Kefah Mokbel

The initiative by the National Institute of Health and Clinical Excellence regarding the potential use of drugs to reduce the risk of breast cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. among high-risk women is greatly welcome. However, the recent publicity regarding the use of Tamoxifen to prevent breast cancer for high-risk women is over-hyped and surprising since there is no new evidence or studies supporting its use in breast cancer prevention.

Tamoxifen was previously shown to reduce the incidenceThe number of new episodes of a condition arising in a certain group of people over a specified period of time. of hormoneA substance produced by a gland in one part of the body and carried by the blood to the organs or tissues where it has an effect.-sensitive (ER positive) breast cancer among high-risk women, however, no significant improvement insurvival was demonstrated. By contrast , tamoxifen has been shown to improve survival in women diagnosed with ER positive breast cancer.

Most breast cancers (80%), which develop in women who carry a BRCA-1 geneThe basic unit of genetic material carried on chromosomes. mutationA change in the genetic material (DNA) of a cell, or the change this this causes in a characteristic of the individual, which is not caused by normal genetic processes., are usually hormone-insensitive (ER-negative) and, therefore, these women are unlikely to benefit from Tamoxifen.

Women with a BRCA-2 gene mutation, usually develop hormone-sensitive (ER positive) breast cancer and therefore they are very likely to derive a significant benefit from drugs such as Tamoxifen, in relation to the incidence of breast cancer, but there is no data to show that Tamoxifen improves survival amongthese women. Women who carry BRCA-1 or BRCA-2 gene mutations are also pre-disposed to ovarianrelating to the ovaries cancer and there is a growing body of evidence that prophylactic salpingo-oophorectomy (removal of the fallopian tubesTwo tubes that transport the egg from the ovary to the uterus. and ovariesFemale reproductive organs situated one on either side of the uterus (womb). They produce egg cells (ova) and hormones in a monthly cycle.) reduces the risk of both ovarian and breast cancer in these women and also improves survival. Therefore, this should be considered as a serious option in women who test positive for these gene mutations. 

Prophylactic mastectomy has been also shown to reduce the risk of developing breast cancer by 90%. Furthermore, oncoplastic breast surgery allows skin-sparing (with or without nipple preservation) and immediate reconstruction with excellent aesthetics thus minimising the impact of mastectomy on women’s body image and quality of life. It is extremely important that we develop molecular (drugs) techniques to allow us to identify women at high risk of developing ER-positive breast cancer since these women will benefit from anti-oestrogenA hormone involved in female sexual development, produced by the ovaries. therapy, such as Tamoxifen. Furthermore, we need to demonstrate, through randomised control trials that such a chemo-preventative strategy would lead to a significant survival benefit prior to recommending these treatments.The potential adverse effectsUndesirable side-effects of medication. of these drugs and their impact on quality of life should be taken into account since they need to ba taken for a long duration starting at a young age for many women.
Biological therapies, such as PARP-inhibitors seem to be promising chemo-preventative agents in women with BRCA gene mutations. It is also important to emphasise the need for regular surveillance, including digital mammographyA diagnostic and screening test using low-dose X-rays to detect breast tumours and MRIAn abbreviation for magnetic resonance imaging, a technique for imaging the body that uses electromagnetic waves and a strong magnetic field. in women who have a geneticRelating to the genes, the basic units of genetic material. predisposition to breast cancer. Finally, these issues underscore the need for an integrated health care system that includes public and GP education programmes, in addition to the further development of benefit/risk assessment tools to guide decision making.

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