In 2010 Robert Schneider, PhD, from New York University's Langone Medical Center received a $50,000 grant from the IBC Research Foundation (ibcRF). Read about this grant.

Dr. Schneider's project, Translating mTOR and Translational Regulation to Therapy in Triple Negative Inflammatory Breast Cancer, has provided the supporting data for continued study of mTOR's role in inflammatory breast cancer (IBC).

At this year's American Society of Clinical Oncology (ASCO) Annual Meeting Dr. Komal Jhaveri presented an outstanding poster on this next phase of the PI3K/AKT/mTOR and JAK/STAT pathway work. Read more about the poster: Hyperactivated mTOR and JAK2/STAT3 pathways: Crucial molecular drivers and potential therapeutic targets of inflammatory breast cancer (IBC). ibcRF continues to work closely with Drs. Jhaveri and Schneider to see this research through to clinical trial.  It's exciting when research funded by ibcRF makes its way to patient care. 

left to right: Eleonora Teplinsky and Komal L. Jhaveri

We've asked Dr. Jhaveri to share about her work and interest in IBC.  Below are her remarks. 

The American Society for Clinical Oncology's Annual Meeting was held in Chicago from May 31-June 4. As one of the Focus on Research Scholars from the Research Advocacy Network, I had more opportunities to attend educational sessions than there were hours in the day! Incidence of HER2-positive breast cancer is between 12-15% overall, but in patients diagnosed with Inflammatory Breast Cancer, the incidence may be as high as 40%. As one whose IBC was triple negative, I decided to increase my understanding of HER-2 and estrogen receptors (ER), and spend a significant amount of time at sessions and poster discussions related to HER-2 and ER.

Central nervous system metastases compose up to 50% of all metastases in HER2-positive breast cancer, according to David A. Cameron, MD, from the University of Edinburgh. Neoadjuvant chemotherapy by itself or trastuzumab (Herceptin) or pertuzumab (Perjeta) without the addition of chemotherapy is inadequate at tackling aggressive HER-2 positive breast cancers. The most active treatment is chemotherapy and an anti-HER2 agent in combination. Dr. Cameron reminded the attendees, "it's not how the cancer responds that's important, but how the patient with the cancer responds."

Trial strategies that focus on high risk disease are especially important, according to Ian Krop MD, PhD from the Dana Farber Cancer Institute. In a precursor to a theme repeated by other speakers at ASCO, Dr. Krop identified the need to study refractory tissue, the importance of obtaining metastatic biopsy specimens, and DNA analysis of circulating tumor cells because a limited number of resistance mechanisms have been validated to date. (IBC certainly fits into the high risk disease category as it is always a locally advanced or metastatic breast cancer with a higher than normal incidence of HER2-positive disease and triple negative disease, and high rate of recurrence.)

George Somio, MD, from the City of Hope Cancer Center, confirmed my understanding of brain metastases from breast cancer: that in triple negative breast cancer patients, the percentage of patients with the brain as the first metastatic site is disproportionately high. The combination of carboplatin and bevacizumab (Avastin) as a treatment for brain metastases is feasible, according to a phase II trial. (Read more about Abstract #513, N.U. Lin) 

John Robert Mackey, MD, from the Cross Cancer Institute, commented on posters that tackled the issue of anthracycline and trastuzumab interaction as a cause of increased cardio toxicity. Concomitant or sequential administration of anthracyclines and trastuzumab does not differ in cardio toxicity. Approximately 5% of patients will have a heart ejection factor decline of 15%, which is clinically significant. The HERA trial indicates that the cumulative incidence of cardiac events increases over time. (Read more about Abstract #525, E. De Azambuja)

Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute addressed a topic of particular interest to me--androgen receptors in basal-like (sometimes called triple negative) breast cancer. At the 2011 San Antonio Breast Cancer Symposium, there was a report about androgen receptors and whether AR receptors might have prognostic or predictive value. Androgen receptors are expressed in 32% of basal-like breast cancers, although the threshold for AR positivity was not defined. In early stage breast cancer, the presence of AR+ is a prognostic marker for better outcome, and a very strong such marker in triple negative breast cancers. (Read more about Abstract 528, I. Bozovic-Spasojevic) This is important to African American breast cancer patients because that group has a higher than normal incidence of triple negative, or basal-like, breast cancers especially in younger women. This is also significant for IBC patients, who do not have early stage cancer, but do have a higher incidence of triple negative cancers.

It is important to remember that not everything in standard breast cancer "fits" in IBC, but recent research can influence treatment decisions.

Carol McWilliams is webmaster and newsletter editor for the Inflammatory Breast Cancer Research Foundation. Her personal motto is: "it's all about the RESEARCH!"  

Inflammatory breast cancer (IBC) continues to be identified by the visible symptoms of edema (swelling), erythema (redness), and peau d'orange (orange peel skin).  In spite of numerous advances over the years we still don't have a pathological or molecular diagnostic for the disease.  Since IBC grows in tumor cell clusters in the dermal lymphatics of the skin, radiation is typically given after mastectomy to reduce the chance of recurrent disease in that area.

After treatment for primary disease as the body is healing and recovering from the insults of chemotherapy, surgery, and radiation it's easy for patients to become hyper-vigilant, worrying about every little ache, pain, or other changes.  It is important to pay close attention to the mastectomy scar area and skin of the chest wall since it's possible that cancer cells may be lingering in the skin having evaded the chemotherapy and radiation.  New research indicates that cancer cells may actually become dormant, just waiting for a signal to spring back to life.  Unfortunately we don't understand this potential process and have no model systems for study.

Some patients experience a localized recurrence, often starting near or around the mastectomy scar line.  Some identify it as "a rash", "pimples", "red bumps", etc.  Just as the initial symptoms of IBC vary, so do the presentations of cutaneous (skin) mets.  See examples of skin mets.

Often these skin mets are resistant to treatment, growing and spreading quickly.  Various chemotherapy options can be used, there have been clinical trials of topical treatments, and even the use of heat along with a special chemotherapy.  The University of Michigan Cancer Center  (part of the Translational Breast Cancer Research Consortium) is currently sponsoring a trial using Veliparib with radiation in the treatment of IBC or loco-regionally recurrent breast cancer.  The purpose of this phase I study is to determine the maximum tolerated dose of veliparib that can be given while a patient is receiving radiation therapy to the chest wall and regional nodes.  A secondary outcome is to describe the nature of toxicity that develops when PARP inhibitors are administered concurrently with chest wall radiotherapy.  This is a single arm study so all participants receive the trial treatment.  As with any phase I trial, this is designed to study safety of the treatment.  Of course patients will also be evaluated for efficacy but that's not part of the primary or secondary outcomes to be evaluated.  Outcomes from phase I trials often influence the direction of subsequent clinical trials with a given agent.  Unfortunately patients who have had prior radiation therapy to the chest wall or regional nodes are excluded from the study. Read more about this study.

The struggles to control skin metastasis are what lead the Inflammatory Breast Cancer Research Foundation to set aside funds for a grant that focuses on skin mets.  Kathleen Livingston, a dedicated IBC research advocate, underwent nearly constant treatment for almost 13 years in an effort to control skin mets.  Multiple clinical trials would provide brief periods of disease stability but never a durable response.  In spite of numerous open lesions on her chest and back, Kathleen kept active and hopeful.  Eventually spread of the disease to her lungs hastened her death.  The Inflammatory Breast Cancer Research Foundation is currently accepting proposals to study this neglected aspect of IBC.  Once the proposals have been reviewed and evaluated by the Medical Advisory Board a grant recipient(s) will be chosen.  This research was important to Kathleen and while it is too late to change the course of her disease, it's not too late to help others.  If you'd like to contribute to this important work visit:  www.ibcresearch.org/donations-fund-raising/