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11th Annual School of Breast Oncology®

11th Annual School of Breast Oncology®


Resources

PER Pulse™ Recap
Three PER Pulse™ Recaps presenting key topics from the 11th Annual School of Breast Oncology®, which was held on November 7 - 10, 2013. 




PER Pulse™ Recap

PER Pulse™ Recap
Medical Writer: Susan R. Peck, PhD



1 of 3
PER Pulse™ Recap
11th Annual School of Breast Oncology®
Evolving Care for Metastatic Breast Cancer


The intensive 4-day School of Breast Oncology® provides a comprehensive curriculum that covers the diagnosis and treatment of breast cancer with an emphasis on multidisciplinary patient management. This is the first in a series of 3 PER Pulse™ Recaps that will review highlights from this meeting.

One of the areas that is evolving most rapidly is the care of patients with metastatic breast cancer (MBC), and these changing paradigms were addressed in several lectures. Highlights included:
  • Dr. William Gradishar provided an overview of the changing landscape of treatment options for HER2-positive (HER2+) MBC. With the approval of two new agents (pertuzumab and ado-trastuzumab emtansine [T-DM1]) since 2012, choices have expanded dramatically and sequencing considerations have become more complex. National Comprehensive Cancer Network guidelines now list trastuzumab plus pertuzumab, in combination with either docetaxel or paclitaxel, as the preferred frontline chemotherapy regimen, based on the demonstrated overall survival (OS) benefit in the CLEOPATRA trial. For patients with disease that has progressed on a trastuzumab-containing regimen, T-DM1 is a new option. In the EMILIA trial, T-DM1 significantly improved both progression-free survival (PFS) and OS compared with capecitabine plus lapatinib. More recently, the TH3RESA trial showed that T-DM1 was also superior to physician’s choice of treatment for patients who had previously received ≥2 HER2-targeted therapies for advanced disease, including trastuzumab and lapatinib, confirming the efficacy of this new agent and the utility of continuing HER2-targeted therapy.
     
  • Dr. Ruth O’Regan presented a discussion on hormone-dependent MBC. Dr. O’Regan emphasized the need to rebiopsy recurrent breast cancers, due to the discordance in receptor status between primary and metastatic disease in approximately 15% of cases.  For patients with hormone receptor-positive (HR+) MBC, endocrine therapies are the preferred initial treatment and may be used through subsequent lines of therapy in responsive patients, reserving chemotherapy for life-threatening visceral disease or exhaustion/failure of endocrine options. The use of targeted therapies to overcome endocrine resistance is also demonstrating utility. The addition of trastuzumab or lapatinib to an aromatase inhibitor (AI) has been shown to improve PFS compared with endocrine therapy alone in patients with HER2+, HR+ MBC, while the addition of everolimus to exemestane improves PFS in patients with HR+ disease that progressed on a nonsteroidal AI. An emerging class of agents, CDK4/6 inhibitors such as palbociclib, has also demonstrated promising activity in combination with endocrine therapy, and several of these agents are currently being investigated in phase II or III trials.
     
  • Dr. Alison Stopeck reviewed chemotherapy options for hormone-independent MBC, particularly triple-negative breast cancer (TNBC). Although much research is being done to understand the molecular subtypes of TNBC and to explore targeted approaches, at present this information should not drive treatment decision making outside of a clinical trial. Instead, factors such as number and type of prior therapies, disease-free interval from adjuvant therapy, and the patient’s performance status and comorbidities should guide treatment choice. For the majority of patients with hormone-independent disease, sequential single-agent chemotherapy is as effective as combination therapy but with less toxicity, and combinations should be reserved for those situations when a rapid response is needed.
Other presentations that dealt with the topic of managing MBC included:
  • Managing CNS Disease by Dr. Paul Sperduto
  • Managing Skeletal Metastases by Dr. Alison Stopeck
  • The Art of Managing Metastatic Breast Cancer by Dr. Melody Cobleigh



2 of 3
PER Pulse™ Recap
11th Annual School of Breast Oncology®
Strategies for Adjuvant and Neoadjuvant Therapy in Breast Cancer

The intensive 4-day School of Breast Oncology® provides a comprehensive curriculum that covers the diagnosis and treatment of breast cancer with an emphasis on multidisciplinary patient management. This is the second in a series of 3 PER® Pulse™ Recaps that will review highlights from this meeting.
 
The optimal systemic management of patients with early-stage breast cancer is a perennial topic of debate, and requires thoughtful, individualized decision making. Current standards and areas of controversy were addressed in several lectures. Highlights included:
  • Dr. Joyce O’Shaughnessy’s lecture on insights into adjuvant chemotherapy. Breast cancer is now recognized as a heterogenous disease, with distinct subtypes that differ in their sensitivity to cytotoxic chemotherapy, and Dr. O’Shaughnessy emphasized the need to individualize treatment decisions. For patients with biologically aggressive breast cancers, the most effective chemotherapy should be used regardless of age, and a regimen containing an anthracycline, cyclophosphamide, and a taxane is the standard of care. For patients with indolent, estrogen receptor-positive (ER+) breast cancers, the benefit of chemotherapy beyond suppression of ovarian function is less clear, and several trials (TailoRx; MINDACT; RxPonder) are ongoing to address the optimal approach for this patient subgroup.  Finally, results from the CALOR trial showed that patients with locally recurrent ER- disease benefit from adjuvant chemotherapy.   
  • Dr. Joseph Sparano’s review of treatment options for locally advanced breast cancer (LABC). Preoperative systemic chemotherapy is the standard of care for inoperable (eg. inflammatory) or operable LABC, and remains an option for operable disease when cytoreduction is indicated. The addition of anti-HER2 therapy in HER2+ disease enhances efficacy. In September 2013, pertuzumab received accelerated FDA approval as neoadjuvant therapy in combination with docetaxel and trastuzumab, based on results from the NeoSphere trial which showed a significant increase in pathologic complete response rates for the triplet compared with docetaxel plus trastuzumab.  Finally, while preoperative endocrine therapy has less potential for cytoreduction than chemotherapy, it is a reasonable option for elderly patients with large tumors or chemotherapy-resistant disease (eg, lobular carcinoma). 
Other lectures dealing with the topic of managing early-stage breast cancer included:
  • Emerging Therapies for Triple-Negative Breast Cancer by Dr. Joseph Sparano
  • Adjuvant Endocrine Therapy for Postmenopausal Hormone Receptor-Positive Breast Cancer by Dr. William Gradishar
  • Adjuvant Endocrine Therapy for Premenopausal Hormone Receptor-Positive Breast Cancer by Dr. Joyce O’Shaughnessy
  • Weight Loss and Exercise by Dr. Anne McTiernan
  • Emesis and Myelosuppression by Dr. Frankie Ann Holmes




3 of 3
PER Pulse™ Recap
11th Annual School of Breast Oncology®
Biomarkers and Breast Cancer Subtypes


The intensive 4-day School of Breast Oncology® provides a comprehensive curriculum that covers the diagnosis and treatment of breast cancer with an emphasis on multidisciplinary patient management. This is the third in a series of 3 PER Pulse™ Recaps that will review highlights from this meeting.
 
Genomic and molecular research has revealed that breast cancer is a heterogenous disease, composed of at least 4-5 main subtypes, which can be further broken down into distinctive subgroups with differing sensitivities to therapeutic agents. Biomarkers such as the estrogen receptor (ER) and HER2 receptor already play an important role in the selection of treatments, and other assays and markers are being investigated for their utility in personalizing therapy. Several lectures focused on these topics, and highlights included:
  • Dr. Anne Moore’s lecture on biologic subtypes and prognostic factors. One point of emphasis was that prognostic factors tell us about the risk of recurrence, while predictive factors tell us about the likelihood a tumor will respond to a specific therapy. Classic prognostic factors include stage, grade, and lymphovascular invasion. Some factors are both prognostic and predictive, such as the estrogen and HER2 receptors. Online decision-making tools such as Adjuvant! Online can help to estimate the risk of recurrence for individual patients. Gene expression assays such as the 21-Gene Recurrence Score and the 70-Gene Prognostic Signature provide additional prognostic information and are being used to help guide treatment decisions for patients with early-stage breast cancers. Genomic assays are also being used increasingly to identify and define distinct intrinsic subtypes of breast cancer, including luminal A, luminal B, basal-like, HER2-enriched, and claudin-low.

  • Dr. Soonmyung Paik’s lecture on predictive biomarker testing. ER expression has been well established as a predictor of sensitivity to endocrine therapies, and Allred scoring refines quantification by immunohistochemistry. Mutation of the ER gene is emerging as a cause of acquired endocrine resistance. When it comes to predicting benefit from adjuvant chemotherapy, the 21-Gene Recurrence Score has been shown to be predictive in ER-positive, HER2-negative, node-negative breast cancers, with high recurrence scores deriving a large benefit, and low recurrence scores deriving little if any benefit. HER2 expression or amplification predicts for sensitivity to HER2-targeted agents, and accuracy of test results has been associated with the volume of assays a lab performs. The American Society of Clinical Oncology and the College of American Pathologists published updated recommendations for HER2 testing and interpretation in November 2013. There is also increasing recognition that ER and HER2 receptor status can differ between the primary tumor and metastases, making rebiopsy of metastatic sites an important component of managing patients with disease recurrence.
Other lectures dealing with the topic of breast cancer biology and biomarkers included:
  • Biology of Breast Carcinogenesis by Dr. David Euhus
  • Pathology of Lobular and Ductal Preneoplasia by Dr. Syed Hoda
  • Matching Evolving Molecular Diagnostics with Novel Therapeutic Agents by Dr. Pamela Munster


Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

This activity is not approved for AMA PRA Category 1 Credit™.

Supported by educational grants from Celgene Corporation, Eisai Inc., Genentech, Lilly USA, LLC and Novartis Pharmaceuticals Corporation.
 







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