Adjuvant Therapy for Receptor-Positive Multifocal Breast Cancer?
Adjuvant Therapy for Receptor-Positive Multifocal Breast Cancer?
A premenopausal 42-year-old woman with a negative family history was found to have 3 separate foci of infiltrating grade 2 ductal carcinoma in the left breast following left mastectomy. The tumor was node-negative, but ER-positive and PR-positive. What further line of management would you suggest?
This case involves a premenopausal 42-year-old woman with multifocal early-stage breast cancer. Her tumor is ER- and PR-positive and lymph node-negative. She is now finished with definitive breast surgery (ie, mastectomy) and presents for further discussion regarding treatment options. We are not given the size of the primary tumor.
The mainstay of adjuvant treatment for this patient is endocrine therapy. Because she is premenopausal, tamoxifen is the agent of choice, and would be expected to substantially reduce her risk of recurrence and improve her chance of long-term survival.
The question is whether to add treatment to tamoxifen. The options that could be added are either adjuvant chemotherapy (which would have a strong likelihood of inducing temporary or permanent amenorrhea) or ovarian suppression.
Randomized trials such as The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-20 have demonstrated that tamoxifen and chemotherapy achieves superior results for women with ER-positive, node-negative breast cancer than does tamoxifen alone; the improvements in disease-free and overall survival are on the order of 3% to 5% in long-term follow-up. Younger women (< age 50) and women with larger tumors (> 2 cm) derive greater benefit from the addition of chemotherapy to tamoxifen than do older women or patients with smaller tumors, owing to their greater risk of tumor recurrence. However, it is not known how much of the benefit of adjuvant chemotherapy in young women actually arises from ovarian suppression secondary to chemotherapy. In this regard, the relative benefits of tamoxifen + chemotherapy vs tamoxifen + ovarian suppression are being directly compared in the Premenopausal Endocrine Responsive Chemotherapy (PERCHE) trial, which is being conducted globally under the leadership of the International Breast Cancer Study Group (IBCSG).
An alternative treatment would be to consider ovarian suppression and tamoxifen. Randomized studies have shown that ovarian suppression can reduce risk of recurrence by similar magnitudes as CMF-based chemotherapy, although in these trials patients were typically not given tamoxifen. The role of ovarian suppression in addition to tamoxifen is being evaluated by the Suppresson of Ovarian Function Trial (SOFT), also led by the IBCSG, which compares tamoxifen alone, tamoxifen + ovarian suppression, or ovarian suppression + an aromatase inhibitor.
My recommendation for this patient would be strongly influenced by the size of the primary tumor. For a tumor 2 cm or greater, or a tumor associated with significant lymphatic-vascular invasion, I would recommend adjuvant chemotherapy, followed by tamoxifen. For a smaller tumor with a more favorable prognosis, I would consider tamoxifen alone, tamoxifen + ovarian suppression, or tamoxifen + chemotherapy, following a conversation with the patient reviewing the risk of recurrence, the available options, the likely benefits of treatment, the anticipated side effects of therapy, and the patient's personal preferences for therapy.
A premenopausal 42-year-old woman with a negative family history was found to have 3 separate foci of infiltrating grade 2 ductal carcinoma in the left breast following left mastectomy. The tumor was node-negative, but ER-positive and PR-positive. What further line of management would you suggest?
This case involves a premenopausal 42-year-old woman with multifocal early-stage breast cancer. Her tumor is ER- and PR-positive and lymph node-negative. She is now finished with definitive breast surgery (ie, mastectomy) and presents for further discussion regarding treatment options. We are not given the size of the primary tumor.
The mainstay of adjuvant treatment for this patient is endocrine therapy. Because she is premenopausal, tamoxifen is the agent of choice, and would be expected to substantially reduce her risk of recurrence and improve her chance of long-term survival.
The question is whether to add treatment to tamoxifen. The options that could be added are either adjuvant chemotherapy (which would have a strong likelihood of inducing temporary or permanent amenorrhea) or ovarian suppression.
Randomized trials such as The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-20 have demonstrated that tamoxifen and chemotherapy achieves superior results for women with ER-positive, node-negative breast cancer than does tamoxifen alone; the improvements in disease-free and overall survival are on the order of 3% to 5% in long-term follow-up. Younger women (< age 50) and women with larger tumors (> 2 cm) derive greater benefit from the addition of chemotherapy to tamoxifen than do older women or patients with smaller tumors, owing to their greater risk of tumor recurrence. However, it is not known how much of the benefit of adjuvant chemotherapy in young women actually arises from ovarian suppression secondary to chemotherapy. In this regard, the relative benefits of tamoxifen + chemotherapy vs tamoxifen + ovarian suppression are being directly compared in the Premenopausal Endocrine Responsive Chemotherapy (PERCHE) trial, which is being conducted globally under the leadership of the International Breast Cancer Study Group (IBCSG).
An alternative treatment would be to consider ovarian suppression and tamoxifen. Randomized studies have shown that ovarian suppression can reduce risk of recurrence by similar magnitudes as CMF-based chemotherapy, although in these trials patients were typically not given tamoxifen. The role of ovarian suppression in addition to tamoxifen is being evaluated by the Suppresson of Ovarian Function Trial (SOFT), also led by the IBCSG, which compares tamoxifen alone, tamoxifen + ovarian suppression, or ovarian suppression + an aromatase inhibitor.
My recommendation for this patient would be strongly influenced by the size of the primary tumor. For a tumor 2 cm or greater, or a tumor associated with significant lymphatic-vascular invasion, I would recommend adjuvant chemotherapy, followed by tamoxifen. For a smaller tumor with a more favorable prognosis, I would consider tamoxifen alone, tamoxifen + ovarian suppression, or tamoxifen + chemotherapy, following a conversation with the patient reviewing the risk of recurrence, the available options, the likely benefits of treatment, the anticipated side effects of therapy, and the patient's personal preferences for therapy.
