The limits of chemoprevention of breast cancer

According to a study presented at the American Cancer Congress (ASCO 2011), aromasine could reduce the risk of breast cancer by 65% ​​in postmenopausal women at risk. Is this a miracle prevention? we makes the point beyond the ad effects.

A reduction in cancer risk of 65%!

Breast cancer accounts for one third of new cases of cancer in women. Rare before 30 years, it is more common between 60 and 65 years and causes 20% of female deaths by cancer, just over 11,500 women. If prevention of screening mortality remains a priority, a new tool could soon complete the preventive arsenal.

Beware of ad effects!

Even if breast cancer can occur at any age, its risk of occurrence increases with aging. It doubles approximately every 10 years until menopause. In addition, other risk factors are identified, such as the presence of a family history, the presence of predisposition genes (BRCA1 or BRCA2 in particular), the presence of Lesions known as atypical or abnormal ...

In order to prevent these cancers, apart from life-style guidelines whose effect is limited, and prophylactic mastectomy (ablation of breasts for women with a very high genetic predisposition for breast cancer), the character of which is very radical, The other option is to prevent precancerous lesions from progressing to invasive cancers. Knowing that these cancers are hormone-dependent, chemoprevention aims to block the production of estrogens after menopause. In the United States, certain anti-estrogens known today as Specific Estrogen Receptor Modulators (SERMs) - tamoxifen and raloxifene - thus have this indication of prevention recognized by the Food and Drug Administration after demonstrating a reduction in the risk of cancer respectively 50% and 38% after 5 years of treatment 2. However, despite significant but rare side effects (endometrial cancer and venous thrombosis), their use remains limited.3 These molecules have not been approved with this indication In the United States.

Along with the development of anti-estrogens, aromatase inhibitors act by preventing the production of estrogens from androgens in the adrenal gland. This effect is related to their ability to block the enzyme (aromatase) responsible for this transformation. These compounds have demonstrated their effects in prevention of relapses and contralateral cancers in postmenopausal women and are thus preferred to anti-estrogens in these women because of less toxicity 4. It then seemed logical to study their effects in chemoprevention Of breast cancer. This is done with the study presented at the American Cancer Congress (ASCO 2011) 5 and published in The New England Journal of Medicine 6. The study named MAP.3 included 4,560 post-menopausal women at high risk Breast cancer (age over 60 years, presence of atypical lesions, in situ cancer sometimes treated with mastectomy, high Gail score - risk assessment based on age of first menstrual period, first child, family history, Biopsy, etc.). Half were treated with aromatase inhibitors, exemestane (Aromasine ®), and the other was given placebo. After an average follow-up of 3 years, researchers identified 11 cases of breast cancer in women under exemestane and 32 cases in women receiving placebo. This corresponds to a reduction in the risk of invasive breast cancer by 65%. Side effects (hot flushes, insomnia, joint pains) are more common under exemestane but have not had a significant impact on the quality of life of treated women. More serious health problems (bone fracture, osteoporosis, hypercholesterolemia, cardiovascular events) are rare and identical in both groups, but the duration of follow-up is limited.

Should this medication be prescribed for all postmenopausal women tomorrow? No.

In spite of the enthusiasm of the principal author of the study, it is therefore not yet advisable to systematically prescribe this product before having data on the long term. Several trials are underway with other aromatase inhibitors, as stated by Professor Pascal Pujol of the CHU Arnaud de Villeneuve (Montpellier), responsible for the MAP.3 trial in the United States 7: "There is a significant need for New preventive drugs at a time when advances in genetics, imaging and biopsy make it possible to better identify high-risk women Two trials involving women at risk for BRCA1 genetic predisposition and BRCA2, which is the highest identifiable risk, promoted in the United States by R & D Unicancer, are underway: the LIBER trial, similar to the MAP.3 assay with another aromatase inhibitor, letrozole, and IBIS2 , An English preventive test that tests a third molecule of the same class, anastrazole.The aim of these studies is to provide these women with a preventive alternative to breast surgery (preventive mastectomy). >

1 - BMJ, Volume 321, September 2000, p.624-628 (abstract available online); 2 - American Society of Clinical Oncology Clinical Practice Guidance on the Use of Pharmacologic Interventions including Tamoxifen, Raloxifene, and Aromatase Inhibition for Breast Cancer Risk reduction. - Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, Morrow M, Runowicz C, Pritchard KI, Hagerty K, Arun B, Garber J, Vogel VG, Wade JL, Brown P, Cuzick J BS, Lippman SM, American Society of Clinical Oncology. - J Clin Oncol. 2009 Jul. 1,27 (19): 3235-58. Epub 2009 May 26 (article available online) 3 - Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. - Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, Bevers TB, Fehrenbacher L, Pajon ER, Wade JL 3rd, Robidoux A, Margolese RG, James J, Runowicz CD, McCaskill-Stevens W, Ford LG, Jordan VC, Wolmark N, National Surgical Adjuvant Breast and Bowel Project. - Cancer Prev Res (Phila). 2010 Jun, 3 (6): 696-706. Epub 2010 Apr 19 (article available online); 4 - American Society of Clinical Oncology Clinical Practice Guideline update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. - Burstein HJ, Griggs JJ, Prestrud AA, Temin S. - J Oncol Pract. 2010 Sep, 6 (5): 243-6. Epub 2010 Aug 6. (article available online); 5- Exemestane for primary prevention of breast cancer in postmenopausal women: NCIC CTG MAP.3-A randomized, placebo-controlled clinical trial. - Abstract LBA504 - ASCO 2011 - (available online) 6 - Exemestane for Breast-Cancer Prevention in Postmenopausal Women. - Goss PE, Ingle JN, Alés-Martinez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, McTiernan A, Robbins J, Johnson KC, Martin LW, Winquist E, Maunsell E, Farmer P, Gelmon KA, Tu D, Richardson H, NCIC CTG MAP.3 Study Investigators. - N Engl J Med. 7 - Exemestane reduces risk of breast cancer in postmenopausal women at high risk by 65% ​​- Unicancer News Release - June 6, 2011. < Code>

UNICANCER, a hospital group dedicated exclusively to the fight against cancer. UNICANCER brings together the 20 Centers for the Control of Cancer (CLCC): private, non-profit institutions, providing a triple mission of care, research and training in the field of oncology. >
First, this study involved women at risk for breast cancer, not all postmenopausal women for whom this treatment was not evaluated. The identification of women at risk is one of the challenges of chemoprevention of breast cancer. Models already exist on the Atlantic coast for tamoxifen and raloxifene, they will have to be developed for exemestane. It is also to be hoped that advances in genetics will enable us to more precisely identify at-risk women who will be able to benefit fully from one molecule (for example, the creation of "bio-banks" collecting tumor samples and characteristics The second is that the long-term side effects of this drug are not known today, just as the optimal duration of administration is unknown.