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13th Annual International Congress on the Future of Breast Cancer®

13th Annual International Congress on the Future of Breast Cancer®


Resources

13th Annual International Congress on the Future of Breast Cancer®: Meeting-in-a-Box
The Meeting-in-a-Box components are designed for you to share the information with colleagues, fellows, and other health care professionals.

PER Pulse™ Recap
Three PER Pulse™ Recaps presenting key topics from the 13th Annual International Congress on the Future of Breast Cancer®, which was held on July 17 - 19, 2014.



PER Meeting in a Box


Presentation Title Faculty Discussion Question
Highlights of Clinical Breast Cancer Management in 2013/2014 Kathy Albain, MD Should one change his/her approach to adjuvant endocrine therapy for premenopausal ER+ patients based on recently reported clinical trial results (SOFT/TEXT)? Should we be applying POEMS trial results to all premenopausal ER-negative patients with (neo)adjuvant chemotherapy? What are the implications of the ALTTO trial to neoadjuvant therapy?
Determining the Risk of Late Recurrence Joseph Sparano, MD How do you define late recurrence? By subtype? Does efficacy of systemic therapy vary by relapse pattern? What biomarkers prognosticate for late recurrence? Are they actionable?
Clinical Implications of Promiscuous Steroid Hormone Receptors Carol Lange, PhD What are the clinical implications of estrogen receptors (ER) and progesterone receptors (PR)? How does PR expression affect ER+ tumor progression? Is PR connected to cyclin D1 expression?
ESR1 Mutations in MBC: Iatrogenic or Clonal Outgrowth?
Faculty has not granted permission to post this presentation
Suzanne A W Fuqua, PhD How do breast cancers become resistant to endocrine therapies? What are the implications of mutations in ESR1/Era? Is acquired resistance the driving mechanism of tumor progression or is metastatic potential the biologic driver? Do primary mutations in ESR1 cause a different effect to treatment from acquired resistance?
Selecting Patients and Managing Toxicity with mTOR Inhibitors Hope S. Rugo, MD Can we predict who will benefit from mTOR inhibitors in the clinic? What are the implications of stomatitis? How important are baseline radiographic assessments for patients with breast cancer treated with everolimus and exemestane? How do you accurately identify noninfectious pneumonitis? Are drug interactions common with this regimen?
Are Adjuvant Bisphosphonates a New Standard of Care? Adam Brufsky, MD, PhD, FACP Can use of adjuvant bisphosphonates affect disease recurrence? Does it affect all recurrence or just bone metastases? Does the menopausal status of the patient affect whether adjuvant bisphosphonates affect disease recurrence?
Novel Inhibitors of Endocrine Therapy Resistance Lori J. Goldstein, MD What are the common mechanisms of resistance to endocrine therapy? What clinical trial results do we have for new endocrine therapy combinations in breast cancer? How do CDK4/6 inhibitors affect estrogen receptor-positive breast cancer? Do CDK4/6 inhibitors, SRC inhibitors, andogen inhibitos, or HDAC inhibitors influence endocrine resistance?
Intraoperative Radiotherapy: A New Standard of Care? David E. Wazer, MD, FASTRO How apparent is the distribution of residual disease during/after surgery? What is accelerated partial breast irradiation (APBI)? What are the types of APBI and how significant an effect does APBI have on disease recurrence?
Does Biology Dictate Risk of Locoregional Recurrence? Eleftherios Mamounas, MD, MPH, FACS What aspects should be included in the risk assessment for locoregional disease recurrence? Does molecular subtype vary the risk? Can we use response to neoadjuvant chemotherapy to predict risk of locoregional recurrence?
New Insights into Surgical Management of Locoregional Disease David M. Euhus, MD, FACS How frequently is the nipple involved with breast cancer? What effect do residual terminal duct-lobular units have on surgery? How do local recurrence rates compare between skin-sparing and nipple-sparing mastectomies? What factors predict response rates to neoadjuvant chemotherapy? What are the uses for sentinel lymph node biopsies before and after neoadjuvant chemotherapy?
Can Radiation Replace Surgery in Some Patients?
Faculty has not granted permission to post this presentation
Lori J. Pierce, MD, FASTRO When/in what patients is it appropriate to use radiation instead of surgery in patients with breast cancer? What are the potential benefits of re-excision, and when is re-excision the best answer?
Does Locoregional Therapy for the Primary Tumor Benefit Patients With Stage IV Breast Cancer? Seema A. Khan, MD In randomized trials, does locoregional therapy for the primar tumor benefit patients with stage IV breast cancer? When is primary site local therapy appropriate?
Who Does Not Need Radiation Therapy? Reshma Jagsi, MD  What elements are involved in patient selection for radiotherapy? How does one predict individual patients that can successfully avoid radiotherapy after breast cancer surgery?
Is Preoperative Therapy the Standard of Care? Frankie Ann Holmes, MD, FACP Should neoadjuvant chemotherapy be standard of care for HER2+ patients? In what patients can pathological complete responses be correlated with event-free survival? What is the prognostic ability of neoadjuvant chemotherapy for HER2+ patients?
Clinical Utility of HER2 Tyrosine Kinase Inhibitors Joyce O'Shaughnessy, MD What specific roles do HER2 tyrosine kinase inhibitors have in therapy? For what patients might benefit from lapatinib plus trastuzumab letrozole without chemotherapy? Does endocrine therapy have a role in the chemotherapy-less group? What is the role of neratinib (pan-HER tyrosine kinase inhibitor), and what adverse event is associated with this regimen?
Novel Insights into Adjuvant Therapy Ruth O'Regan, MD Are we overtreating small HER2+ breast cancers? Do all HER2+ breast cancers need trastuzumab and chemotherapy? What role does endocrine treatment play in HER2+ adjuvant therapy?
PIK3CA Mutations in HER2+ Breast Cancer Sara Hurvitz, MD How frequent are PIK3CA mutations in breast cancer, and how frequently are PIK3CA mutations a mechanism of trastuzumab resistance? Are PIK3CA mutations prognostic in patients with HER2+ breast cancer, and does the estrogen receptor play a role in this prognostication? Are certain HER2-targeted agents not affected by PIK3CA mutations?
Sequencing Therapies in HER2+ Metastatic Breast Cancer Debu Tripathy, MD Which trials looked at HER2-targeting agents in firstline vs secondline vs later-lines? Can HER2-enriched triple negative breast cancer be treated effectively with HER2-targeting agents? With our current knowledge, what agents can and should we use in a purposed sequential manner?
Clinical Utility of Community-Based Molecular Profiling Joyce O'Shaughnessy, MD Which targeted agents are effective only in highly selective populations vs those with more broad activity? Is molecular profiling by next-generation sequencing of clinical utility to community oncologists?
Preoperative Platinum: A New Standard of Care? William Sikov, MD For what patients has neoadjuvant platinum chemotherapy been most beneficial? What are the roles of BRCA mutation status and Homologous Recombination Deficiency (HRD) scores in treatment choice? Which platinum is the best choice for triple negative breast cancer? Do platinums have a role as adjuvant therapy?
Novel Preoperative Therapy Hypotheses Jenny Chang, MD How should tumor heterogeneity and cancer stem cell gene signatures play into treatment decisions? Are nitric oxide signaling (NOS) inhibitors viable therapy options for metastatic breast cancer? Can tumor-infiltrating lymphocytes (TILs) be used as a marker for platinum sensitivity?
Moving Beyond BRCA1/2 Germline Testing Claudine Isaacs, MD What genes besides BRCA1/2 are associated with hereditary breast cancer syndromes? What are the pros and cons associated with next-generation sequencing? What specific breast cancer genes should clinicians be testing for? What should be done for screening and prevention of cancer in patients with mutations that put them at higher risk for breast cancer?
Obesity, Fats and Sugar: The Evolving Science David M. Euhus, MD, FACS What data exists comparing fat/fatty acid consumption and breast cancer incidence or outcome? How do patients with higher body mass indexes (BMIs) compare in breast-cancer-specific survival to those with lower BMIs? Does insulin resistance change a person's risk for breast cancer?
Metastatic TNBC: Are Cytotoxic Agents Subtype-Specific? Joyce O'Shaughnessy, MD Is there a way to classify/subtype triple negative breast cancer (TNBC) that is clinically useful? Are there cytotyoxic agents with greater benefit in TNBC than other types of breast cancer?
Incorporating Imaging into Locoregional Management Nola M. Hylton, PhD How should magnetic resonance imaging (MRI) be used for evaluating the local extent of disease? Is MRI more or less effective for evaluating axillary disease? How does one use quantitative imaging as a biomarker?
Cancer Care and Oncology Practice: Now and in 2015 Linda Bosserman, MD, FACP What do the rising costs of cancer care mean for community oncology practice? How do we achieve optimal outcomes and drive value and quality care? How do we use standarization (pathways, etc) while still individualizing treatment? What are vs what should be the data that is driving decisions in practice?



PER Pulse™ Recap PER Pulse™ Recap
Medical Writer: Beth Cameron, PhD


1 of 3
PER Pulse™ Recap
13th Annual International Congress on the Future of Breast Cancer®

The 13th Annual International Congress on the Future of Breast Cancer® was held on July 17-19, 2014, in Huntington Beach, California. The congress brought together breast cancer experts from across the country to discuss the clinical impact and implications of genetic and phenotypic subtyping, novel agents, strategies, and improved regimens that are changing the future of breast cancer therapy. This first of 3 PER Pulse Recaps focused on the congress examines select data presented on hormone receptor-positive (HR+) and locoregional breast cancers. Presentations by Kathy Albain, MD, FACP, on clinical highlights of early-stage breast cancer trials from the past year; David Euhus, MD, FACS, on the surgical management of locoregional disease; and Reshma Jagsi, MD, PhD, on patient selection for radiation therapy (RT) are summarized.

Dr. Albain started the conference with a discussion of the implications of data from recently reported clinical trials in early-stage breast cancer treatment, including the Tamoxifen and Exemestane Trial (TEXT), the Suppression of Ovarian Function Trial (SOFT), the Prevention of Early Menopause Study (POEMS), and the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) study. Only the first two will be discussed here. Discussion of the remaining trials and additional details from TEXT and SOFT can be found at the following links: faculty presentations; presentation slides.

TEXT (NCT00066703) and SOFT (NCT00066690) are ongoing randomized, open-label phase III trials examining adjuvant therapy in premenopausal HR+ early breast cancer. Joint results from these 2 trials, presented at the 2014 meeting of the American Society of Clinical Oncology and in an article in The New England Journal of Medicine, provide context for the role of aromatase inhibitors (AIs) for women treated with ovarian-function suppression (OFS; triptorelin, oophorectomy, or ovarian irradiation) up to 12 weeks after surgery. In a joint analysis of 4690 women at a median 5.7 years of follow-up, 5-year disease-free survival (DFS) rates were 91.1% for the exemestane-plus-OFS arm and 87.3% for the tamoxifen-plus-OFS arm (P <.0002). Similarly, an analysis of breast cancer- and distant recurrence-free survival (RFS) intervals at 5 years showed statistically significant superiority for exemestane: differences of 4% (overall hazard ratio [HR] = 0.66; P <.0001) and 1.8% (HR = 0.78; P =.02), respectively. No significant difference in overall survival (OS) rates was observed at this time. Overall rates of grade 3/4 targeted adverse events were similar between groups, and the safety profile was comparable to those in postmenopausal women in other trials.

In contrast, another phase III trial, conducted by the Austrian Breast and Colorectal Cancer Study Group (ABCSG-12; NCT00295646), showed similar DFS, RFS, and OS between the AI anastrozole-plus-OFS arm (with goserelin) and the tamoxifen-plus-OFS arm after a median follow-up of 62 months. Long-term OS was actually statistically worse with the AI in this trial (HR = 1.75; P =.02). In the neoadjuvant setting, response rates were superior with anastrozole plus OFS to those with tamoxifen plus OFS (both with goserelin) among HR+ premenopausal women enrolled in the randomized phase III STAGE trial (NCT00605267): 70% for anastrozole versus 51% for tamoxifen.

Dr. Albain concluded that exemestane plus OFS should be an option for appropriate premenopausal patients with HR+ breast cancer, but that it is not yet the standard of care. Additional follow-up will be needed to determine whether an OS benefit can be shown, and this regimen requires consideration of toxicities. She also pointed out the need for caution because of the discordance with results of ABCSG-12. Further, the subset of patients with no prior chemotherapy did just as well with tamoxifen as with the AI in the SOFT/TEXT joint analysis, whereas the higher-risk chemotherapy-requiring group had greater benefit from exemestane. SOFT also had another arm of tamoxifen without OFS, and Dr. Albain believes that the comparison of this group with the group receiving tamoxifen plus OFS would be useful to determine whether to add OFS to tamoxifen or switch to an AI plus OFS for premenopausal patients currently on tamoxifen. Another consideration is weighing the potential benefits to premenopausal women of an additional 5 years of tamoxifen versus those of switching to an AI after 5 years of tamoxifen when patients become postmenopausal, as assessed in the MA.17 trial (NCT00754845).

Dr. Euhus discussed the surgical management of locoregional disease, including lumpectomy margins, nipple-sparing mastectomies, and surgery after neoadjuvant chemotherapy (NAC). Prompted by controversy over optimal tumor-excision margins, the Society of Surgical Oncology and the American Society for Radiation Oncology recently published a meta-analysis and consensus guidelines for stage I and II invasive breast cancer on breast-conserving surgery (BCS) and systemic treatment. The guidelines define acceptable margins as “no ink on the tumor,” as this is associated with low rates of ipsilateral breast tumor recurrence, and may lead to decreased reexcision rates (currently approximately 25%), improvements in cosmetic outcomes, and reduced costs. The joint statement concluded that neither RT nor adjuvant therapy can “fix” positive margins, that all tumor subtypes benefit from negative margins, that neither the presence of lobular cancer nor the age of the patient warrants wider margins, and that tumors with extensive intraductal components may warrant wider margins.

Regarding nipple-sparing mastectomy, Dr. Euhus emphasized that this is of greater concern now than it has been in the past, because more women are opting for complete (and, increasingly, bilateral) mastectomy. The nipple is involved in about 15% of cancer cases, and 9% to 26% of women have terminal duct-lobular units in the nipple-areola complex. Local recurrence rates, however, are similar for skin- and nipple-sparing mastectomies. Dr. Euhus’s primary selection criterion for nipple-sparing mastectomy is the lack of nipple involvement. He pointed out that previous breast irradiation is not a contraindication, and RT can be administered after completion of the reconstruction.

Dr. Euhus stated that for certain patients, NAC can expand surgical treatment options. A joint analysis of the National Surgical Adjuvant Breast and Bowel Project Protocol B-27 (NCT00002707) and B-18 trials examined predictors of locoregional recurrence after NAC with doxorubicin-cyclophosphamide (AC) or AC followed by docetaxel followed by surgery. After 10 years of follow-up with 3088 patients, predictors of locoregional recurrence included clinical and pathological node status. The primary predictor among lumpectomy patients was age, and among mastectomy patients it was pretreatment clinical tumor size. Because of these data, the results of other trials, and his own experience, Dr. Euhus believes that pretreatment axillary sonography and/or needle biopsy is indicated. For clinically node-negative patients, sentinel lymph node (SLN) biopsy after NAC, although slightly less accurate than before NAC, preserves valuable prognostic information and may obviate the need for axillary dissection. For clinically node-positive patients, pretreatment site-of-disease markers are important, and a very thorough SLN biopsy should be considered to determine clinical complete response (cCR), with axillary dissection and clinical trials as options if cCR is not achieved. He pointed out that residual nodal disease after NAC is different from a positive SLN biopsy before NAC.

Dr. Jagsi explained the rationale for postsurgical RT, including that it helps prevent locoregional recurrence, which can be physically and psychologically traumatic and costly, and that it has a positive impact on survival. On the other hand, RT is not without cost, morbidity, and burden to patients, so the optimal scenario would be identifying patients who would benefit from RT and sparing those at low risk after surgery and systemic therapy. Various randomized trials have compared BCS outcomes between patients with invasive disease or ductal carcinoma in situ who did and did not receive RT. Based on these results, it is Dr. Jagsi’s opinion that women with stage I disease who are older than 70 years of age, adherent to endocrine therapy, and willing to participate in routine surveillance may consider omission of RT after lumpectomy. For now, however, post-BCS RT remains the standard of care for all other women.

Danish and Canadian trials, as well as the Early Breast Cancer Trialists’ Collaborative Group trial, have established that patients with 4 or more positive lymph nodes derive a clear benefit from postmastectomy RT, and there is accumulating evidence of benefit for all node-positive patients. Further research is needed, however, and individualized risk assessment for every patient is critical. The relative risks and benefits of postmastectomy RT should be explained to all patients with positive lymph nodes or high-risk node-negative features, and a radiation oncologist should be involved in these discussions.


2 of 3
PER Pulse™ Recap
13th Annual International Congress on the Future of Breast Cancer®

The 13th Annual International Congress on the Future of Breast Cancer®, held July 17-19, 2014, in Huntington Beach, California, brought together breast cancer experts from across the country to discuss the clinical impact and implications of genetic and phenotypic subtyping, as well as novel agents, strategies, and regimens that are changing the future of breast cancer therapy. This, the second of 3 PER Pulse™ Recaps focused on the congress, summarizes selected data presented on the types and timing of chemotherapy.  Here we presented data from 3 of the discussions. Discussion of topics in their entirety and additional presentations can be found at http://www.gotoper.com/conferences/ibc/meetings/13th-Annual-International-Congress-on-the-Future-of-Breast-Cancer/resources#MIB. A related Community Practice Connections CME activity can be found at http://www.gotoper.com/Link/114.

Highlights of the meeting included the following:
  • Frankie Ann Holmes, MD, discussed the rationale for preoperative chemotherapy for patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer. Dr. Holmes began by proposing that neoadjuvant chemotherapy (NACT) be made the standard of care for patients with newly diagnosed HER2+ breast cancer anticipating surgery, especially in light of the US Food and Drug Administration (FDA) recent approval of the anti-HER2 antibody pertuzumab for NACT (not adjuvant). Thus, this is an opportunity for patients with early breast cancer to receive synergistic dual-target, highly effective, tolerable therapy with the 2 antibodies pertuzumab and trastuzumab, providing them with the possibility of preoperative downstaging to reduce the risk of toxicities such as lymphedema.

    The cardiac safety of the combination was confirmed by the results of the TRYPHAENA study (N=225), in which only 1 patient (0.4%) experienced left ventricular systolic dysfunction, and efficacy was similar to that in other trials. The contribution of pertuzumab was demonstrated by the results of the NeoSphere trial (N=417), in which dual blockade (HER2/HER3) increased the rate of pathologic complete response (pCR), with an acceptable toxicity level. These results formed the basis for the FDA’s accelerated approval of pertuzumab for NACT.

    Another rationale for NACT as standard of care is the ability to predict long-term outcomes for patients with HER2+ breast cancer based on their responses to NACT. The Collaborative Trials in Neoadjuvant Breast Cancer analyzed pooled results of 11,955 patients studied over 21 years, and showed that patients who achieved pCR had a 64% lower mortality risk (95% confidence interval [CI], 0.58-0.69) than did those without pCR. In addition to predicting and improving outcomes for patients who achieve pCR, NACT can help in elucidating the mechanism of treatment resistance in posttherapy residual tumor. This information can be used in identifying targets for new strategies and novel agents, and for supporting accelerated evaluation and approval of these agents.
     
  • Debu Tripathy, MD, addressed various combinations and sequences of chemotherapy for HER2+ metastatic breast cancer (MBC). Dr. Tripathy talked about what is known and what is still being learned about therapy for HER2+ MBC. In early trastuzumab monotherapy trials, the best response rates were seen in patients with no prior cancer treatment, suggesting that trastuzumab is useful for first-line therapy. Lapatinib, on the other hand, has been observed to have potent efficacy in the laboratory but does not perform as well clinically as do antibodies such as trastuzumab, possibly because trastuzumab also activates the immune system. Therefore, lapatinib is not frequently used in practice in the first-line setting.

    Dual HER2 blockade yields clinical benefit, as shown, for example, by higher pCR rates in NACT studies. The combination of trastuzumab plus pertuzumab has yielded higher progression-free survival (PFS) and overall survival (OS) rates than has either MAb alone, with a favorable (including cardiac) toxicity profile. The one notable adverse event (AE) is a higher rate of diarrhea with the combination. Dr. Tripathy frequently gives patients who will be on this regimen prophylactic antidiarrheal agents. Dual blockade has also been shown to be effective in later lines of therapy.

    Trastuzumab emtansine (T-DM1) has been tested in the first-line setting and has been found to yield higher PFS rates and fewer AEs than did a combination of trastuzumab plus docetaxel. More definitive trials of this novel agent in first-line therapy are pending. T-DM1 has been studied more extensively as second-line therapy. In the EMILIA study, T-DM1 was compared with the old standard for second-line therapy, capecitabine plus lapatinib. Both PFS (P <.0001) and OS (P =.0006) rates were higher with T-DM1. The TH3RESA study compared T-DM1 with physician choice of therapy for patients with multiple previous lines of therapy. Median PFS with T-DM1 (6.2 months) was nearly twice that with other therapies (3.3 months; P <.0001), and OS was also superior with T-DM1 (P ≤.0040).

    Dr. Tripathy pointed out that HER2 and other receptor tyrosine kinases have multiple signaling pathways, which vary from individual to individual. He presented his algorithm, adapted from the National Comprehensive Cancer Network guidelines for treatment of HER2+ MBC and emphasizing personalized therapy. The preferred first-line therapy, in his opinion, is a combination of a taxane, trastuzumab, and pertuzumab. Other options are paclitaxel plus/minus carboplatin, docetaxel, vinorelbine, and capecitabine. For estrogen receptor–positive cancer, first-line options are letrozole plus lapatinib or an aromatase inhibitor plus tamoxifen plus trastuzumab. T-DM1 has become the new standard for second-line therapy, with other options including capecitabine plus lapatinib, trastuzumab plus vinorelbine, and trastuzumab plus lapatinib.

    Dr. Tripathy concluded that the goal is to give patients as many options as possible by identifying which patients would benefit most from which treatments and individualizing therapy, bearing in mind that, for example, triple-negative breast cancer is heterogeneous, including a subset that resembles HER2+ disease. Therapy should be selected based on factors such as patient preferences and circumstances and drug toxicity profiles. Clinicians need to collaborate and share information and should be knowledgeable about open clinical trials and willing to refer their patients to centers where they can take advantage of the studies.
     
  • Joyce O'Shaughnessy, MD, described the positive and negative issues surrounding community-based molecular profiling of patients with breast cancer. Dr. O’Shaughnessy addressed the premise that identifying molecular profiles that predict benefit facilitates selection of patients with a greater chance of benefiting from specific therapies. This premise fits with the current trend toward personalized cancer treatment: The application of molecular diagnostics to a patient’s tissue sample allows identification of active pathways, which in turn permits selection of therapy targeted to the active pathway(s). Some targeted agents are effective in highly selected populations, but others have broader activity, with no need for such specific targeting. For example, in the BOLERO-2 study, the benefit with everolimus was apparent and maintained regardless of whether patients had gene mutations. Thus, clinicians do not need community-based molecular profiling to aim patients toward treatment with everolimus or toward clinical trials of phosphatidylinositol 3-kinase (PI3K) inhibitors.

    The utility of next-generation sequencing (NGS) molecular profiling has been investigated. In one study, use of NGS identified 90% of 169 patients with actionable mutations (ie, ones that can be addressed with either approved or investigational agents). In another study, 28% of 132 patients received different therapies from those originally planned because of NGS results, but for nearly 75% of the patients in this study there were not enough targeted treatment options available. In a phase I trial at MD Anderson Cancer Center, 12 (44%) of 27 patients had complete responses, partial responses, or stable disease for more than 6 months with matched agents, whereas only 2 (20%) of 10 had similar results with unmatched agents. This highlights the fact that coupling profiling with access to a large number of targeted agents would be particularly useful for developing personalized treatment regimens.

    SAFIR01 was a multicenter French study matching genotype with targeted therapy. From 404 biopsies of patients with MBC, the researchers identified 194 targetable genomic alterations. By the time of publication, 48 patients (25% of those with identified targetable genomic alterations and 12% of those biopsied) had received treatment matched to the results of their genomic analyses. Of these 48 patients, 12 (3% of all those biopsied) realized benefit from matched treatment. The SAFIR02 study in HER2-negative MBC is ongoing.

    The issue of whether to inform patients of incidental findings during profiling is a delicate one. The American College of Medical Genetics has developed a list of 57 genes, 23 of which are cancer-related, that should be reported to patients when found, because addressing inherited risk early may prevent serious morbidity or early mortality. The Presidential Commission for the Study of Bioethical Issues recommends anticipating the potential for these issues to come up and giving patients the right to choose whether they want to be informed if they do arise. Dr. O’Shaughnessy believes that if clinical trials are available from which patients might benefit, there may be an obligation to inform them of the risks found and possibilities for addressing them.

    Although the use of genotype to identify targeted therapies has great potential, its utility is limited by the appearance of alternate pathways that have not yet been well elucidated. There is a need to capture and disseminate high-quality data.
     

3 of 3
PER Pulse™ Recap
13th Annual International Congress on the Future of Breast Cancer®

The 13th Annual International Congress on the Future of Breast Cancer®, held July 17-19, 2014, in Huntington Beach, California, brought together breast cancer experts from across the country to discuss the clinical impact and implications of genetic and phenotypic subtyping, as well as novel agents, strategies, and regimens that are changing the future of breast cancer therapy. This, the third of 3 PER PulseTM Recaps focused on the congress, summarizes selected data from 3 presentations on preoperative chemotherapy, the effect of patient factors on breast cancer outcomes, and techniques that can be used in selecting therapy and monitoring its effects. More detailed discussion of these and other presentations can be found at http://www.gotoper.com/conferences/ibc/meetings/13th-Annual-International-Congress-on-the-Future-of-Breast-Cancer/resources#MIB, as well as videos of the presentation accompanied with the slides. A related Community Practice Connections CME activity can be found at http://www.gotoper.com/Link/114.

  • William M. Sikov, MD, pointed out that platinum-based chemotherapy has been studied and used for more than 25 years. It has shown efficacy in metastatic breast cancer, but for treatment-naïve patients only, and it comes with significant toxicity; therefore, it had been largely ignored until recently. Interest in platinum-based chemotherapy increased with the discovery that BRCA1-mutated breast cancers, 75% to 80% of which are triple-negative breast cancer (TNBC), are more sensitive to platinums and gemcitabine, and are less sensitive to taxanes.

    A number of studies using pathologic complete response (pCR) rate as a surrogate end point support the use of platinum-based therapy in BRCA1-mutated breast cancer and TNBC. In a Polish study of 80 patients with BRCA1-mutated breast cancer, neoadjuvant chemotherapy (NACT) with cisplatin resulted in pCR for 68% of patients. The ongoing INFORM study (N=166) is comparing cisplatin and paclitaxel in BRCA1-mutated breast cancer. The majority of studies have addressed the addition of a platinum drug to standard NACT for TNBC. Of several recent studies, only 1 did not show significant improvement in pCR with the addition of a platinum drug to standard NACT with paclitaxel.

    There have been no direct comparisons of platinum drugs in the neoadjuvant setting. A meta-analysis (N=1598) found similar pCR rates with carboplatin and cisplatin, and a pooled analysis of platinum drugs added to docetaxel found higher pCR rates with cisplatin than with carboplatin, but the balance is tipped in favor of carboplatin by its lower toxicity profile. In addition to direct comparisons, studies are needed to determine optimal dosages and schedules, to capture data on long-term recurrence-free survival (RFS) and overall survival (OS), and to confirm results of the Cancer and Leukemia Group B (CALGB) 40603 study suggesting that the addition of carboplatin to NACT increases the percentage of patients with TNBC who may be eligible for breast-conserving surgery (BCS).

    In daily clinical practice outside of trials, Dr. Sikov believes that adding a platinum drug to standard NACT may be appropriate for patients with extensive disease, those who are not candidates for BCS but would like to consider it, and those who cannot take a standard chemotherapy regimen because of underlying disease.
  • David Euhus, MD, noted that the association between high dietary fat intake and breast cancer mortality is not strong. Along with other experts, Dr. Euhus believes that consumption of sugar and refined carbohydrates is a much more significant risk factor. Of the dietary fats, only saturated and trans fats have been shown to be associated with higher mortality rates among patients with breast cancer, and these modest effects are seen in terms of all-cause mortality only. Dr. Euhus favors diets such as the “paleo” diet, which limits carbohydrates and sugar, but not fat intake. He advises his patients to not start the day with a large carbohydrate load, but rather to emphasize protein intake.

    Dr. Euhus stated that consumption of omega-3 fatty acids may be associated with a reduced risk of breast cancer, but patients might need to take higher dosages (eg, 300 mg/d-500 mg/d) than they are willing to consume; also, this protection may be conferred by food sources alone, and the issue of excessive mercury intake with large, fatty fish such as salmon may hamper a solely dietary intake.

    Patient factors also influence breast cancer mortality risk. Data collected by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) on 80,000 patients in 70 trials showed a high association between body mass index (BMI) and breast cancer outcomes among patients with estrogen receptor–positive breast cancer, especially pre- and perimenopausal patients, but not among estrogen receptor–negative patients. Among postmenopausal patients, high proportions of visceral fat are associated with lower rates of pCR (P<.001) and of RFS (P=.01), OS (P<.001), and breast cancer–specific survival (P=.003) after NACT than are lower proportions of visceral fat. Hyperinsulinemia and hyperglycemia have been shown to increase the risk of breast cancer-associated mortality and to increase the risk of breast cancer itself by 15% to 20%, although metformin treatment may reduce the risk.

    Obesity, hyperinsulinemia, hyperestrogenemia, hyperglycemia, and inflammation are conditions that frequently occur together and that interact to increase the risk of breast cancer and mortality. Studies are needed to elucidate these interactions and identify methods of reducing risk, and further the possibility of targeted therapy.

    Dr. Euhus addressed the effects of obesity on treatment for breast cancer. In the ATAC (Arimidex, Tamoxifen Alone or in Combination) study of 172 postmenopausal women with early hormone receptor–positive breast cancer, recurrence rates were higher among patients with higher BMIs. For women with low BMIs, anastrozole was more effective than tamoxifen, but this difference diminished among patients with higher BMIs. The Austrian Breast and Colorectal Cancer Study Group (ABCSG)-06 (postmenopausal) and -12 (premenopausal) trials both found higher survival rates among obese women with tamoxifen alone than with tamoxifen plus an aromatase inhibitor, raising the possibility of a negative aromatase inhibitor effect.
  • Nola Hylton, PhD, discussed the use of magnetic resonance imaging (MRI) at various points in the staging and treatment of breast cancer. MRI is effective in elucidating the extent of disease in primary breast cancer, and thus can be used in the planning of surgery. MRI has demonstrated greater agreement with histopathology than have clinical examination, mammography, and ultrasound, although it has not yet been compared with newer 3-dimensional x-ray or ultrasound techniques. MRI is not as effective in evaluating axillary disease because the contrast uptake is not specific for lymphadenopathy.

    Unfortunately, the accuracy of MRI has not translated into improvements in surgical outcomes. The UK COMICE (Comparative Effectiveness of MRI in Breast Cancer) trial (N=1623) found no difference in reoperation rates between patients who had and had not undergone preoperative MRI studies. It should be noted, though, that the MRI techniques used in this trial were not optimal, and there was no study-specific protocol. A recently opened trial, the Alliance A011104/ACRIN 6694, is comparing the impacts of preoperative MRI and no MRI on rates of local recurrence in TNBC and human epidermal growth factor receptor 2–positive breast cancer.

    MRI also has utility in the management of preoperative therapy. It can be used to help determine which patients are candidates for any surgery and, specifically, for BCS. It is also a sensitive measure of changes in tumors due to therapy, and early predictions of response can trigger a potentially beneficial change in the therapeutic regimen.

    Although MRI is more accurate than other methods, it has been observed to miss residual disease after an apparent excellent response to therapy. In the Translational Breast Cancer Research Consortium (TBCRC) trial 017, a retrospective multicenter analysis of post-NACT MRI data (N=746), MRI showed high overall accuracy (74%) for predicting pCR, but the rate varied among breast cancer subtypes. Thus, Dr. Hylton said, MRI should not be used as the sole method of identifying patients who can be spared surgery.

    MRI is a noninvasive biomarker that can be used to predict response to therapy and patient survival. It can be repeated over time to track change. Another advantage is that it provides immediate feedback, which patients like, thus fostering adherence. For MRI to be used effectively in this setting, however, standardized criteria need to be identified and used consistently.


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., Foundation Medicine, Inc., Genentech, Genomic Health Inc., Lilly, and Novartis Pharmaceuticals Corporation.

For further information concerning Lilly grant funding visit www.lillygrantoffice.com.
 







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