Important research is slated to be presented at the 36th Annual San Antonio Breast Cancer Symposium (SABCS), which will be held on December 10 ? 14, 2013 in San Antonio, Texas. The symposium will bring together physicians and academic (basic) scientists involved in breast cancer in medical, surgical, gynecologic, and radiation oncology, as well as other appropriate health care professionals from around the world to discuss what is new and where the field is headed. The organizers expect 7,500 attendees from more than 90 countries.
Several presentations will address the issue of over-diagnosis, as a result of widespread mammography screening. While studies have shown that screening programs have been effective in lowering breast cancer specific mortality in certain subpopulations of women, false-positive results can lead to unnecessary invasive follow-up procedures and heightened patient anxiety. In addition, screening may also identify malignancies that may never become a significant risk to the patient?s health.
?The issue has become really controversial since the US Preventive Task Force came out with their recommendations, which many found confusing and controversial,? said C. Kent Osborne, M.D, director of the Dan L. Duncan Cancer Center and director of the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston, during a pre-meeting press call.
These? studies will go a long way in helping clinicians decide whether patients should go through surgery to remove the tumor in the breast when faced with metastatic disease…
The Value of Mammography
One of the abstracts being presented (Abstract S1-10) addresses why there have been inconsistent conclusions among studies. An international consortium led by Robert Smith, PhD, of the American Cancer Society, revaluated four major reviews from the US, Europe and the United Kingdom, and according to the SABCS program committee, this paper will present interesting data on the value of mammography. It will also address the issue of overdiagnosis, in regards to mammography studies. [1]
Over-treatment
Another important issue is that of over-treatment, (Abstract S2-01) and researchers will present the results of the Post-operative Radiotherapy In Minimum-risk Elderly 2 (PRIME-2) trial. In this clinical trial, 65 year old women were randomized women to either radiation post surgery or no surgery following lumpectomy. These results will provide oncologists with more data on whether all patients in this subgroup need radiation therapy, which is now the standard of care for those undergoing breast conservation surgery.[2]
Is surgery really necessary?
Two papers have examined another treatment question ? is surgery on the primary tumor necessary for patients who have metastatic disease on diagnosis? (Abstract S2-02 and abstract S2-03) If the cancer has already spread, removing the primary tumor isn?t going to cure the patient, Osbourne commented, so is surgery really necessary? [3][4]
Studies evaluating this issue have largely been retrospective, but these two new trials are prospective and randomized. One of the studies randomly assigned 350 women patients with metastatic breast cancer who have received and responded to chemotherapy to either surgery with subsequent radiation therapy or to no follow-up intervention (Abstract S2-02). The goal of this trial is to help clinicians understand if localized surgery and radiotherapy are beneficial interventions for women with metastatic disease.
The second trial randomized patients with metastatic breast cancer who are treatment-na?ve to receive either surgical resection of their primary tumor or no resection (Abstract S2-03). All patients were then received standard treatment for the metastatic disease. ?These two studies will go a long way in helping clinicians decide whether patients should go through surgery to remove the tumor in the breast when faced with metastatic disease,? Osbourne said.[4]
Breast Cancer Prevention
Breast cancer prevention will also be addressed, and growing research has been looking at blocking estrogen as a means of preventing the disease in women deemed to be at a high risk. Jack Cuzick PhD, from the Wolfson Institute of Preventive Medicine in London, and colleagues, will present the first results of the IBIS-II trial, which is evaluating prevention using the aromatase inhibitor anastrozole in high risk women. (Abstract S3-01). Conducted in the United Kingdom, this large prospective trial randomized 3,800 patients to either anastrozole or placebo, and will address the efficacy of the drug to lower estrogen levels in postmenopausal women at risk. [5]
Tolerability of side effects
The study will not only address the efficacy of this intervention but importantly, tolerability of side effects. One of the problems with preventive chemotherapy is that there is a need for a drug that is relatively without side effects because most women, even those deemed to be at high risk, will not be diagnosed with breast cancer. ?Most of the women will not develop the breast cancer that we?re trying to prevent and the benefit is small, so side effects become a major factor,? Osbourne said. ?I would be surprised if this study is negative, but results will also add additional information on the value of using estrogen deprivation therapy for breast cancer prevention.”
Side effects of the aromatase inhibitors also play a role in treatment compliance among breast cancer patients. Up to 30% of all patients do not complete the five year course of treatment, despite the strong evidence that their use can help prevent disease recurrence. In one study, by Nora Henry MD, and colleagues, from the University of Michigan, looked at baseline symptoms to see if it affected tolerability of side effects. If a woman already has depression or joint stiffness, which are common side effects, are they going to be the ones most likely to be discontinuing treatment?
A related study being presented by Melinda Irwin, PhD, from Yale University, looked at interventions to help side effects. She and her colleagues randomized patients with the most common side effect, arthralgia, to either an exercise program or usual care. They are evaluating to see if a regular exercise program will help reduce arthralgias.
Treatment resistance in a commonly encountered issue in cancer care in general. One new study, using combination therapy in the metastatic setting, will demonstrate one possible route of curbing resistance in hormone-positive disease. Specifically, the data presented will show the results of a trial that combined the aromatase inhibitor letrozole with dasatinib, a drug that targets a potential resistance pathway (Abstract S3-07).[6]
The SABCS program committee members felt that this will be an important study, as it may demonstrate whether or not this combination that simultaneously blocks the estrogen pathway and one escape pathway could improve outcomes in this population.
Neo-adjuvant studies
Neo-adjuvant therapy is being used increasingly in the management of patients, especially those with large and locally advanced breast cancers. This treatment is usually aimed at reducing the size of the primary tumor to eliminate occult systemic metastases in order to improve survival. The FDA recently provided guidance on the use of pathologic complete response (pCR) as a clinical trial endpoint in neo-adjuvant treatment prior to surgery. Since the goal of neoadjuvant systemic therapy is to reduce the probability of remaining metastatic dis
ease after surgical removal of their tumor, pCR is a way to assess tumor response in vivo.
Knowing the neo-adjuvant effects on the tumor prior to tumor resection might be able to predict the long-term effects on micro-metastatic disease. Two presentations at the meeting will analyze the results of neo-adjuvant therapy in women with HER2-positive disease.
In one study, a follow up analysis will of the NeoALTTO trial will be presented, and provide new data on the correlation of pCR in the breast to long-term event free survival (Abstract S1-01). Martine J. Piccart-Gebhart, MD, Ph.D, President of the European Organisation for Research and Treatment of Cancer (EORTC), and colleagues, randomized women with HER2-positive primary breast cancer to receive lapatinib, trastuzumab, or the combination, followed by surgery, chemotherapy, and 1 year of the same therapy that the patient received in the neoadjuvant setting. The authors will report the relationship between pCR and long term event free survival. [7]
?The patients now have been followed long enough to know the correlation between the initial response before surgery and the follow-up,? explained Carlos L. Arteaga, M.D, president-elect of the American Association for Cancer Research (AACR) and associate director for translational/clinical research and director of the Breast Cancer Program at Vanderbilt-Ingram Comprehensive Cancer Center. ?This is anticipated to generate a lot of excitement.?
A second neo-adjuvant therapy trial evaluated a novel chemotherapy combination of docetaxel and carboplatin in addition to lapatinib, trastuzumab, or both (Abstract S1-02). Even though this study seems similar to the NeoALTTO, an important difference is the new chemotherapy backbone. The safety data will be in important, and these two trials may contribute to the growing body of evidence that supports neo-adjuvant therapy without the need to do costly, long adjuvant studies. The implication is that this approach could accelerate the time it takes to approve clinically active drugs. [8]
?This study is important is that it uses a new chemotherapy backbone and the toxicity data of this regimen is going to be very important to learn about,? Arteaga noted.
For more information:
[1] Smith RA, Duffy S, Chen TH-H, Yen AMF, Tabar L. Disparities in the estimates of benefits and harms from mammography: Are the numbers really different? Abstract S1-10
[2] Kunkler IH, Williams LW, Jack W, Canney P, Prescott RJ, Dixon The PRIME 2 trial: Wide local excision and adjuvant
hormonal therapy ? postoperative whole breast irradiation inwomen ? 65 years with early breast cancer managed by breastconservation. Abstract S2-01
[3] Badwe R, Parmar V, Hawaldar R, Nair N, Kaushik R, Siddique S, Navale A, Budrukkar A, Mittra I, Gupta S. Surgical removal of primary tumor and axillary lymphnodes in women with metastatic breast cancer at firstpresentation: A randomized controlled trial. Abstract S2-02
[4] Soran A, Ozmen V, Ozbas S, Karanlik H, Muslumanoglu M, Igci A,Canturk Z, Utkan Z, Ozaslan C, Evrensel T, Uras C, Aksaz E, Soyder A.Ugurlu U, Col C, Cabioglu N, Bozkurt B, Dagoglu T, Uzunkoy A, Dulger U. Early follow up of a randomized trial evaluating resectionof the primary breast tumor in women presenting with de novostage IV breast cancer; Turkish study (protocol MF07-01) Abstract S2-03
[5] S3-01.Cuzick J, Sestak I, Forbes JF, Cawthorn S, Roche N, Mansel RE, von Minckwitz G, Bonanni B, Palva T, Howell A. First results of the International breast cancer interventionstudy II (IBIS-II): A multicentre prevention trial of anastrozoleversus placebo in postmenopausal women at increased risk ofdeveloping breast cancer. Abstract S3-01
[6] Paul D, Vukelja SJ, Holmes FA, Blum J, McIntyre KJ, Kumar AR, Lindquist DL, Osborne CR, Sanchez IJ, Goldschmidt JH, Wang Y, Asmar L, Lee ME, Wu N, Logie K, O?Shaughnessy J. Letrozole plus dasatinib improves progression-free survival (PFS) in hormone receptor-positive, HER2-negative postmenopausal metastatic breast cancer (MBC) patients receiving first-line aromatase inhibitor (AI) therapy. Abstract S3-07
[7] Piccart-Gebhart M, Holmes AP, de Azambuja E, Di Cosimo S, Swaby
R, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios C,
Gelber R, Eidtmann H, Baselga J. The association between event-free survival and pathological complete response to neoadjuvant lapatinib,trastuzumab or their combination in HER2-positive breast cancer. Survival follow-up analysis of the NeoALTTO study (BIG 1-06) Abstract S1-01
[8] Hurvitz S, Miller JM, Dichmann R, Perez AT, Patel R, Zehngebot LM, Allen H, Bosserman LD, DiCarlo BA, Kennedy A, Giuliano A, Calfa CJ, Molthrop DC, et al. Final analysis of a phase II 3-arm randomized trial of neoadjuvant trastuzumab or lapatinib or the combination of trastuzumab and lapatinib, followed by six cycles of docetaxel and carboplatin with trastuzumab and/or lapatinib in patients with HER2+ breast cancer (TRIO-US B07). Abstract S1-02.
Video Programs
Highlights from the 36th SABCS, San Antonio, Texas, USA – December 10 – 14, 2013 [Video Program]
Photo: Professor Martine Piccart, MD, Ph.D, President of ESMO – European Society for Medical Oncology. Photo courtesy: ESMO.
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