The question of the optimal hormonal treatment for premenopausal breast cancer patients whose tumors express the estrogen or progesterone receptor has come under review in recent years. The gold standard Tamoxifen has been the mainstay even since the first reported benefits in the ’80’s. The question of whether adding ovarian ablation to Tamoxifen adds benefit has until very recently been unknown. Two trials, one published in the Journal of Clinical Oncology and the other in the New England Journal of Medicine in early December 2014 help to answer this question. Click on the links to see the abstracts. Dr. Stark can upon request provide the entire articles. In the first (JCO) trial women were given either Tamoxifen alone or Tam plus ovarian ablation (performed either with drugs that block endocrine ovarian function, removal of the ovaries, or radiation to the ovaries). Women all had no node involvement and could not receive chemotherapy. The long term results (average follow up ten years) were the same except that the women whose ovaries were ablated were much more symptomatic. The second (NEJM) trial looked at women with an overall worse prognosis: many of them had positive nodes. Chemo was allowed. If they received chemo, those drugs could not impede ovarian function (for complicated reasons), so as a practical matter the women in this trial were younger than in the first study. This was a three-armed study: Tamoxifen alone, Tam plus ovarian ablation and Exemestane plus ovarian ablation. This latter drug will cause rises in estrogen levels in some premenopausal women so you can’t use it without ovarian ablation; however, it is more potent than Tam. In that study only women with a poorer prognosis to begin with — those who received chemo — benefited from ovarian ablation, and the Exemestane arm did best of all. So, at least for the moment the question has been answered: if you are premenopausal, have hormone-receptor-positive breast cancer, have no lymph nodes involved and otherwise enjoy a good prognosis, take Tamoxifen only. If your prognosis in more guarded, take Exemestane and have your ovaries ablated, and just accept the additional side effects. Dr. Stark comments, “These two studies taken together are a huge help. A cautionary note is the expected accelerated osteoporosis in women taking Exemestane. The authors did not examine this issue but it will be an issue for those women. They need to take preventive measures from the outset and have their bones evaluated regularly.”