Ovarian suppression combined with the anti-estrogen drug Aromasin® (exemestane) appears to greatly reduce the risk of breast cancer recurrence in younger women according to the results of the Suppression of Ovarian Function Trial (SOFT) presented at the 2014 San Antonio Breast Cancer Symposium in Texas. These results were also published online simultaneously in The New England Journal of Medicine.
Estrogen causes some cancers to grow. The breasts, uterus and other female organs are composed of cells that contain estrogen receptors. When cells that have estrogen receptors become cancerous, exposure to estrogen increases the cancer’s growth. Cancer cells that have estrogen receptors are referred to as estrogen receptor-positive (ER-positive) cancers.
The growth of ER-positive breast cancer cells can be prevented or slowed by reducing the exposure to estrogen. This is the goal of the hormonal drug tamoxifen and the newer aromatase inhibitors; Femara® (letrozole), Arimidex® (anastrazole), and Aromasin. In premenopausal women, surgical removal of the ovaries or suppression of ovarian activity may also be used to reduce estrogen exposure.
Earlier this year, initial results of the SOFT trial combined with the Tamoxifen and Exemestane Trial (TEXT) were presented at the 2014 American Society of Clinical Oncology Annual Meeting and also published in The New England Journal of Medicine. The combined results of the TEXT and SOFT studies demonstrated that Aromasin is more effective than tamoxifen in preventing breast cancer recurrence in young premenopausal women who also receive post-surgical treatment to suppress ovarian function.
The SOFT clinical trial was designed to assess the value of ovarian suppression in 3,066 young women with hormone receptor–positive breast cancer. In this study, doctors from the International Breast Cancer Study Group compared three treatments; tamoxifen, tamoxifen plus ovarian suppression, and Aromasin plus ovarian suppression administered for 5 years. Ovarian function suppression was achieved by use of monthly injections of the GnRH agonist Trelstar® (triptorelin), surgical removal of both ovaries, or radiation therapy to the ovaries. Women could also receive chemotherapy as part of their overall treatment plan if they were at higher risk of recurrence.
Overall, women who did not require chemotherapy did well. Five-year survival without cancer recurrence was 95.8% if treated with tamoxifen alone, 95.1% with tamoxifen plus ovarian suppression, and 97.1% with Aromasin plus ovarian suppression.
However, premenopausal women treated with chemotherapy and ovarian suppression added to tamoxifen achieved a 22% reduction in the risk of recurrence compared to tamoxifen alone and the combination of Aromasin plus ovarian function suppression was even better. The Aromasin treated women experienced a 35% risk reduction for recurrence versus tamoxifen alone. The proportion of women surviving 5 years without cancer recurrence was 78% for tamoxifen alone, 82.5% for tamoxifen plus ovarian suppression, and 85.7% for Aromasin plus ovarian function suppression.
In women 35 years and younger treated with chemotherapy, the 5-year breast-cancer-free rate was 67.7% in those on tamoxifen alone, 78.9% in those on tamoxifen plus ovarian suppression, and 83.4% in those on Aromasin plus ovarian suppression.
Women who underwent ovarian suppression had better results than those taking tamoxifen alone. And the benefits were most pronounced in women younger than 35. However, the best results were seen when ovarian suppression was paired with Aromasin.
The results of this trial have changed the treatment paradigm; women who are at low risk, have smaller tumors, negative nodes, are older, and have not received chemotherapy but are still premenopausal can be reasonably and well treated with tamoxifen alone.
For women who are clearly at high risk, particularly those who are under 35 years of age, ovarian suppression appears to provide a clinically meaningful reduction in breast cancer recurrence. The reduction is significantly greater when the ovarian suppression is added onto Aromasin.
For the remaining women at intermediate risk, such as those with small tumors but positive nodes or larger tumors but low grade, women have a choice whether to use ovarian suppression with endocrine therapy or tamoxifen alone, and need to make this decision with their doctor.
The trial confirms that Aromasin combined with ovarian suppression is effective treatment for premenopausal women and superior to tamoxifen. These results are consistent with earlier studies evaluating ovarian suppression combined with Aromasin and provide a new treatment option for young women with hormone-sensitive breast cancer.2
Franics P, REgan M, Felmin G, et al. Randomized comparison of adjuvant tamoxifen (T) plus ovarian function suppression (OFS) versus tamoxifen in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Analysis of the SOFT trial. Presented at the 2014 San Antonio Breast Cancer Symposium. December 9-13, 2014. San Antonio Texas. Abstract S3-08.
 Franic P, Regan M, Fleming G, et al. Adjuvant Ovarian Suppression In Premenopausal Breast Cacer. New England Journal of Medicine. Early Online Publication December 11, 2014.
 Pagani O, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. NEJM early online. June 1, 2014. ASCO late breaking abstract #1.
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