Ask The Expert--Breast Cancer
A 46-year-old perimenopausal female with inflammatory breast cancer had been treated with modified radical mastectomy; 23 lymph nodes were positive, and her tumor was strongly positive for estrogen and progesterone receptors and HER2/neu. She completed adjuvant chemotherapy with doxorubicin/cyclophosphamide followed by paclitaxel, followed by radiation therapy. What should be the next step? Should I treat her with a combination of docetaxel/trastuzumab for 6 months followed by another 6 months of trastuzumab alone? Or should I put her on tamoxifen alone?
This is a case of locally advanced, inflammatory breast cancer (T4) with multiple positive lymph nodes (N3). She has a worrisome prognosis. Her tumor is described as hormone receptor-positive, and HER2-positive. She has received doxorubicin/cyclophosphamide and paclitaxel chemotherapy in the adjuvant setting, along with regional radiation therapy. She was perimenopausal at the time of diagnosis.
Based on the recent results from the adjuvant trastuzumab trials, I would offer this patient 1 year of adjuvant trastuzumab therapy. It is notable that the NSABP and Intergroup trials, as well as the HERA trial, excluded patients with inflammatory or stage IIIB breast cancer. However, it would seem that the adjuvant principles from the studies of node-positive patients should apply in this case. Based on the results of the HERA trial, it seems reasonable to offer trastuzumab after completion of adjuvant chemotherapy and radiation therapy. That strategy lowered the risk of recurrence by 46% in the short follow-up period of 1 year presented at the ASCO meeting. Because of the increased risk of cardiotoxicity, I would recheck left ventricular ejection fraction (LVEF) before beginning trastuzumab therapy, and then continue to monitor LVEF regularly during the year-long course of treatment. Also, given the high-risk nature of her tumor, I would consider restaging this patient before starting trastuzumab.
There are no data to support the use of sequential docetaxel after adjuvant paclitaxel treatment for breast cancer. I would offer trastuzumab monotherapy, not concurrent therapy with docetaxel.
In addition to initiating anti-HER2 therapy, it is critical not to forget antiestrogen therapy. As a perimenopausal woman, this patient is a candidate for therapy with tamoxifen. Aromatase inhibitor therapy is not effective in pre- or perimenopausal patients. Most of the data for women with estrogen receptor-positive and HER2-positive tumors reported in the NSABP/Intergroup/HERA trials were derived from patients receiving tamoxifen and trastuzumab, so the safety experience of this combination is well characterized.
Finally, I would consider adding ovarian suppression (OS) to the adjuvant treatment for this patient. While the benefits of OS, added to tamoxifen and chemotherapy, are not well characterized -- and certainly have not been characterized in conjunction with trastuzumab therapy -- a variety of indirect evidence suggests that OS may lower the risk of recurrence. Given the very high-risk nature of this patient's clinical presentation, it would be reasonable to consider adding OS.
A 46-year-old perimenopausal female with inflammatory breast cancer had been treated with modified radical mastectomy; 23 lymph nodes were positive, and her tumor was strongly positive for estrogen and progesterone receptors and HER2/neu. She completed adjuvant chemotherapy with doxorubicin/cyclophosphamide followed by paclitaxel, followed by radiation therapy. What should be the next step? Should I treat her with a combination of docetaxel/trastuzumab for 6 months followed by another 6 months of trastuzumab alone? Or should I put her on tamoxifen alone?
This is a case of locally advanced, inflammatory breast cancer (T4) with multiple positive lymph nodes (N3). She has a worrisome prognosis. Her tumor is described as hormone receptor-positive, and HER2-positive. She has received doxorubicin/cyclophosphamide and paclitaxel chemotherapy in the adjuvant setting, along with regional radiation therapy. She was perimenopausal at the time of diagnosis.
Based on the recent results from the adjuvant trastuzumab trials, I would offer this patient 1 year of adjuvant trastuzumab therapy. It is notable that the NSABP and Intergroup trials, as well as the HERA trial, excluded patients with inflammatory or stage IIIB breast cancer. However, it would seem that the adjuvant principles from the studies of node-positive patients should apply in this case. Based on the results of the HERA trial, it seems reasonable to offer trastuzumab after completion of adjuvant chemotherapy and radiation therapy. That strategy lowered the risk of recurrence by 46% in the short follow-up period of 1 year presented at the ASCO meeting. Because of the increased risk of cardiotoxicity, I would recheck left ventricular ejection fraction (LVEF) before beginning trastuzumab therapy, and then continue to monitor LVEF regularly during the year-long course of treatment. Also, given the high-risk nature of her tumor, I would consider restaging this patient before starting trastuzumab.
There are no data to support the use of sequential docetaxel after adjuvant paclitaxel treatment for breast cancer. I would offer trastuzumab monotherapy, not concurrent therapy with docetaxel.
In addition to initiating anti-HER2 therapy, it is critical not to forget antiestrogen therapy. As a perimenopausal woman, this patient is a candidate for therapy with tamoxifen. Aromatase inhibitor therapy is not effective in pre- or perimenopausal patients. Most of the data for women with estrogen receptor-positive and HER2-positive tumors reported in the NSABP/Intergroup/HERA trials were derived from patients receiving tamoxifen and trastuzumab, so the safety experience of this combination is well characterized.
Finally, I would consider adding ovarian suppression (OS) to the adjuvant treatment for this patient. While the benefits of OS, added to tamoxifen and chemotherapy, are not well characterized -- and certainly have not been characterized in conjunction with trastuzumab therapy -- a variety of indirect evidence suggests that OS may lower the risk of recurrence. Given the very high-risk nature of this patient's clinical presentation, it would be reasonable to consider adding OS.
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