Metastatic Breast Cancer: 2012 Is the Time of Hope and Optimism
In the beginning…our surgeons ruled the world of cancer. No matter how big or small, no matter the location, with or without symptoms, a surgical biopsy was in the cards. A palpable “lump” in the breast or calcium deposits seen on mammogram was no exception. A tissue diagnosis has always been among the first steps to get to the etiology. As we look back to 2011, we find of the 1.8 million cases of cancer in our country, over 200,000 were female breast cancer, unfortunately with 40,000 deaths in the last year . 85 percent are Stage I and II disease, meaning only local involvement as confined to the breast or in the draining adjacent axillary lymph nodes. The remainder have local regional Stage III presentations or metastatic distant disease with bone, lung, liver, adrenal gland, and brain the most common sites of distant or Stage IV disease.
Prior to the Fall of 1972, at the time of the first ABIM certification exam in Medical Oncology, surgeons had already realized that female breast cancer was a systemic disease. In fact the beginning of “adjuvant chemotherapy” was a practice by surgeons at Yale New Haven that included a single dose of intravenous Cytoxan chemotherapy just prior to surgery. Despite multiple modifications of the primary surgical intervention, whether it was Radical Mastectomy versus Modified Radical Mastectomy or Extented Radical Mastectomy, there was still a significant number of patients who relapsed with recurrent breast cancer as many as 30 years after the surgery. Radiation therapy was common after any of the surgeries proposed with some benefit to prevent local recurrence but a high proportion of difficult to manage lymphedema on the mastectomy side of surgery. Two important advances in surgical technique limited the amount of surgery popularized by Hellman et al, at Dana Farber Cancer Center, which was the “lumpectomy” for tumors less than 2.0 cm around the areola that also received iridium implants into the site of the lumpectomy with external beam radiation after lymph node dissection. Those patients with axillary lymph nodes containing cancer received chemotherapy as well.
Despite less surgery but integrated radiation and chemotherapy, there were still over 20 percent of patients at risk for recurrence and death from metastatic disease. Remember that prior to 1972, we had no tumor markers, no estrogen or progesterone receptors to help guide our therapeutic choices. Therefore surgery was likewise the treatment of choice for metastatic disease especially for the premenapausal woman that had only surgical therapeutic options available to them such as oophorectomy, and with response adrenalectomy, and with response trans-sphenoidal hypophysectomy that often led to post operative electrolyte dysfunction ( Diabetes Insipidus ). At that time, however, the search for an anti-estrogen was uncovered to cause a medical oophorectomy or adrenalectomy without need for surgery. Subsequently with the risk of secondary malignancies, and venous thrombosis, great efforts were made to develop the aromatase inhibitors. At that time, the median survival of these patients with metastatic breast cancer was one year.
Few studies demonstrate survival advantage for combination chemotherapy in metastatic disease as opposed to single sequential chemotherapy; however, there may be significant improvement in response and duration of response with Targeted therapy and the class of biologics that are often given together with chemotherapy. As of this ASCO, we have now a nano-particle taxane and non taxane chemotherapy for metastatic breast cancer that individually has produced increased survival in patients previously treated for metastatic breast cancer. At ASCO 2010, we had initial data to support in an Italian study that in first line metastatic breast cancer, once a complete or partial response occurs that you should continue therapy for that patient and not offer a “drug holiday.” This is because in this randomized trial the patients with response that continued on chemotherapy had a survival advantage as opposed to those who had a break in their chemotherapy once a response was seen. The discovery of antigenic determinants that are over expressed in metastatic breast cancer will continue to serve the important role of using the molecular biology of the tumor in the treatment against the tumor. Herceptin therapy is an example in the adjuvant trials where four trials now demonstrate decreased recurrence and increased survival for Her-2 Neu positive breast cancer treated with Herceptin and chemotherapy combinations for one year. The overexpression of GP-60, Cavalein, and “Sparc” intra-tumor receptors in metastatic breast cancer may occur in up to 50-60 percent of patients and may be predictive of whom shall respond to albumin-labeled taxane. Our excitement, however, comes from median survivals improved from one year for metastatic breast cancer to now over five years for the average patient with advanced disease and is accompanied by improved quality of life with the majority of life spent as an outpatient. The multi-discipline approach to the diagnosis and therapy of breast cancer at both the basic science and clinical science levels, will have given us the opportunity to continue to make a positive difference in the quality and quantity of life of our patients with metastatic breast cancer in 2012.