The San Antonio Breast Cancer Symposium is the largest scientific meeting devoted to breast cancer, attracting national and international attention. It is attended by clinicians, researchers and advocates. “The Symposium aims to achieve a balance of clinical, translational, and basic research, providing a forum for interaction, communication, and education for a broad spectrum of researchers, health professionals, and those with a special interest in breast cancer.”
This year, Dr. Robert Miller, a medical oncologist at Johns Hopkins University specializing in the care of breast cancer patients and a regular participant in the #BCSM tweet chats, attended the conference. Here are some of the studies he felt were most relevant to our community, with his interpretation of the results.
S1-03. Adding bevacizumab (Avastin) to chemotherapy and trastuzumab (Herceptin) for patients with HER2 positive breast cancer – “BETH” trial
[Article link: http://ascopost.com/ViewNews.aspx?nid=10838]
This trial looked to answer the important question of whether the outcome for women with early-stage (non-metastatic) HER2+ breast cancer could be improved by adding the drug bevacizumab (Avastin) to a combination of chemotherapy and trastuzumab (Herceptin), the current standard adjuvant therapy, which is given following lumpectomy or mastectomy. Bevacizumab is a drug that is useful in the treatment of cancers of the colon, lung, kidney, and brain, but its role in breast cancer has been more controversial. Still, it was thought to be important to test it since its blocks the development of new blood vessels in tumors, a phenomenon known to be important in women with HER2+ cancers and associated with a poorer prognosis. In this study, over 3500 patients with HER2+ breast cancer were randomly assigned to a standard chemo/trastuzumab regimen alone (in 92% of cases it was “TCH” – docetaxel, carboplatin, and trastuzumab) or to the same regimen plus bevacizumab given IV every 3 weeks. After three years of follow up, it was determined that, disappointingly, adding the bevacizumab did not improve disease-free survival, which was 92% for both groups. Side effects, including bleeding, hypertension, and bowel perforation, were greater in the bevacizumab group, and that group also had a slightly higher risk of congestive heart failure, a known complication of trastuzumab. The good news was that the overall survival rates at 3 years – still early in follow up – was 96-97% for both groups, so patients were generally doing well.
BOTTOM LINE: Adding bevacizumab to chemo/trastuzumab did not lower the chance of breast cancer recurrence as hoped, and it added more side effects, so it is not a therapy that should be used in this situation. The study also showed that the standard TCH regimen was highly effective for HER2+ breast cancer, highlighting the dramatic improvements for this subtype compared to the era before the routine use of trastuzumab pre-2005.
S5-07. Using measurements of Circulating Tumor Cells (CTCs) in blood to guide chemotherapy in metastatic breast cancer – SWOG S0500
[Article link: http://www.onclive.com/conference-coverage/sabcs-2013/Level-of-CTCs-Prognostic-But-Not-Helpful-In-Switching-Therapy-in-Metastatic-Breast-Cancer]
Breast cancer tumor cells traveling in the bloodstream (CTCs) can be measured by a variety of sophisticated techniques, including the CellSearch assay, and high numbers have been associated with a poor prognosis for patients with metastatic breast cancer. Although this test has been available for several years, there is a lot of uncertainty as to whether it should be used to guide treatment. In this trial, patients with metastatic breast cancer who had not yet started chemotherapy and who had a CTC level of 5 or greater were treated with their first chemo cycle and then had a second CTC level done. If the second level was less then 5, they continued on the same chemo, but if greater than 5, they were then randomly assigned either to stay on the same chemo or to switch to a different chemo of their doctor’s choosing. In the study, 286 patients had a second CTC level of 5 or more, so 123 stayed on the same chemo and 123 were switched. Unfortunately, the “switchers” did no better than those who stayed on the same chemo, and the median survival was 12 months for both (i.e., about half of the patients lived more than 12 months and half less). By comparison, the patients who had fewer than 5 CTCs at first measurement had the longest survival, with a median of 35 months, and those who had CTC > 5 at first measurement but dropped to CTC < 5 after one cycle of chemo had an intermediate median survival of 23 months.
BOTTOM LINE: The CTC test was not helpful in guiding chemotherapy choices as demonstrated in this trial, so this test should not be used to determine if chemo is “working.” Rather, oncologists should continue to rely on traditional measurements of effectiveness (symptoms, physical exam findings, scans) to guide treatment. The CTC test, when elevated at baseline prior to the first dose of chemo, can identify patients who have a particularly poor prognosis, although, frustratingly, it is not clear how they should then be managed.
S3-01. Using anastrozole to reduce the risk of a first breast cancer in postmenopausal women – IBIS-II trial
[Article link: http://www.medpagetoday.com/MeetingCoverage/SABCS/43383]
This trial looked to answer the question whether the aromatase inhibitor (AI) drug anastrozole (Arimidex) was able to reduce the risk of a first breast cancer in postmenopausal women who did not have the disease but who were at high risk. The population studied was women age 40-70 who were at an increased risk of developing breast cancer on the basis of a positive family history, increased breast density, or a prior biopsy showing atypia or lobular carcinoma in situ (LCIS). Over 3800 such women were randomized 50:50 to receive anastrozole 1 mg daily x 5 years or a matching placebo. After a median follow-up of 5 years, 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer, which translated to a 53% reduction in risk. Looking specifically at ER+ invasive cancers, there were 20 (1%) in the anastrozole group and 47 (2%) in the placebo group, again a reduction of about half. As expected in a trial with short follow up, there was no evidence that survival rates were higher in the anastrozole group. Side effects such as hot flashes/night sweats were seen in both groups (49% for placebo, 57% for anastrozole), perhaps not as great a difference as expected. The same was true for joint pain (46% placebo, 51% anastrozole).
BOTTOM LINE: The role of anastrozole and other AIs in women with a diagnosis of breast cancer is unquestioned, but that is not what this study addressed. This trial is the second to show that taking an AI reduces the incidence of breast cancer in women who don’t have the disease but are high risk (the first was the 2011 MAP.3 trial which used exemestane), and older data show that both tamoxifen and raloxifene are also effective in risk reduction. The real question is, “Is it worth it?” To date, none of these four drugs has been shown to improve overall survival, and it isn’t clear if the ER+ breast cancers being prevented are likely to be those that would be harmful in the first place, enough to offset the inconvenience and potential side effects of taking a pill for 5 years. On the other hand, with more than 230,000 women in the U.S. projected to develop invasive breast cancer in 2013, even a reduction of <1% could be significant. But clearly, more study and long term follow up are required before AIs can be recommended routinely for risk reduction.
S2-02, S2-03. The role of surgical resection of the primary tumor in women presenting with metastatic breast cancer.
[Article link: http://www.medpagetoday.com/MeetingCoverage/SABCS/43441]
Two trials, one from India and one from Turkey, looked at the question of whether or not it is helpful to remove the primary tumor via mastectomy or lumpectomy in women whose breast cancer is already metastatic at the time of diagnosis. Previous data have been inconclusive, with some studies showing a small benefit and others not, some even suggesting it might be harmful. In the Indian trial presented by Dr. Badwe, patients with metastatic breast cancer were treated with standard chemo upfront, and those showing a response were then randomly assigned to undergo standard local treatment (mastectomy or lumpectomy, +/- radiation) or not. Unfortunately, the overall survival rates were essentially identical in both groups (21 vs. 19 months), and there was even a suggestion that the patients who had surgery had a higher rate of distant recurrences. In the trial from Turkey presented by Dr. Soran, patients were randomized upfront to standard surgery vs chemotherapy and no upfront surgery. Disappointingly, the median survival was not statistically improved in women who underwent surgery. A possible benefit was seen for upfront surgery in women with a single bone metastasis, although the numbers were very small and longer follow up is required to be definitive.
BOTTOM LINE: Based on these two trials, for women whose breast cancer is diagnosed at Stage IV and who don’t have any specific symptoms caused by the primary tumor (such as pain or bleeding), there is no proof that doing surgery on the primary site improves long term outcomes, even if it lowers the chance of the cancer getting worse on the chest wall. However, more research is needed to determine if this applies to all types of breast cancer, all patients regardless of demographics, and all sites of metastases. There are several ongoing trials in the U.S. and internationally attempting to answer this question more conclusively, and the 10-15% of women whose cancer is first diagnosed at Stage IV are encouraged to participate.
Many thanks to Dr. Miller for this post! Feel free to leave comments or ask for clarification of any of the studies summarized here. For more from Dr. Miller, here’s the link to his blog and follow him on Twitter.
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