Breast Cancer


Breast cancer, a disease in which malignant cells form in tissues of the breast, is the most common type of cancer (other than skin cancer) among women. Less than 1 percent of breast cancer occurs in men. The risk of getting breast cancer increases with age. Inherited gene mutations and a family history of this disease also may increase risk.    

At Ohio State's Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James), a multidisciplinary team of medical, surgical and radiation oncologists, as well as breast reconstruction surgeons and rehabilitation therapists, creates research-based treatment plans tailored to each patient's type of breast cancer.

In 2011, the OSUCCC – James opened the Stefanie Spielman Comprehensive Breast Center,  the first of its kind in the Midwest to offer in one location the full continuum of breast cancer care—from prevention and screening through detection, diagnosis, treatment and survivorship. The center is named for an Ohio State University alumna, philanthropist and breast cancer patient who worked for more than 10 years to heighten public awareness of breast cancer and to raise money for breast cancer research at Ohio State, before her death in 2009 at age 42.

As one of only four institutions approved by the National Cancer Institute (NCI) to conduct phase I and II clinical trials on NCI-sponsored anticancer agents, the OSUCCC – James has access to more leading-edge, targeted cancer therapies than most hospitals across America. That translates to better outcomes, fewer side effects and more hope. ​

Research Strengths

  • Evaluating new targeted therapies for breast cancer;
  • Designing innovative clinical trials that efficiently combine novel and standard anticancer agents for breast cancer and its complications;
  • Applying translational and basic science findings to develop more effective therapies for breast cancer.

Grants

Omega-3 Fatty Acids and ERPR(-) and HER-2/NEU(+) Breast Cancer Prevention
Funded by the National Cancer Institute (1R01CA164019-01A1)
PI: Lisa Yee, MD
Objectives:

  • Determine the effects of dietary-3 fatty acids on biomarkers of exposure and response in women at high risk for recurrent estrogen receptor, progesterone receptor breast cancer +/- HER-2/neu overexpression
  • Define the role of dietary-3 polyunsaturated fatty acids (PUFAs) in the epigenetic regulation of the inflammatory responses underlying mammary carcinogenesis as a novel mechanism for the effects of omega-3 PUFAs
  • Development of these biomarkers of omega-3 PUFA exposure and response will enable the assessment of this bioactive food component in future large-scale prevention trials for women at risk for recurrence of ERPR(-)HER-2/neu(+) or triple negative breast cancer

Breast Cancer Survivors’ Cardiovascular Risks: Treatment and Behavioral Influences
Funded by the National Cancer Institute (1R01CA186720-01)
PI: Janice Kiecolt-Glaser, PhD
Objectives:

  • Prospectively evaluate the impact of chemotherapy treatment on postprandial responses to a high saturated fat meal in women diagnosed with breast cancer
  • Assess relationships between depression and postprandial responses to a high saturated fat meal before and after cancer treatment
  • Appraise the relative impact of chemotherapy-related changes in menopausal status, cardiorespiratory fitness and central adiposity as correlates and predictors of postprandial responses
  • Evaluate treatment-related postprandial responses to a high saturated fat meal as predictors of coronary artery calcification scores. Data from this study will improve understanding of the enhanced cardiovascular risks associated with both chemotherapy and depression, and thus may lead to new models for assessment and treatment

Social Modulation of PTEN in Women
Funded primarily by an “Idea Grant” from Pelotonia, an annual grassroots bicycle tour that raises millions of dollars for cancer research at the OSUCCC – James.
PIs: Maryam Lustberg, MD; Courtney Devries, PhD; Cynthia Timmers, PhD
Objectives:

  • Examine whether loneliness and isolation alter cancer-related gene activity in breast cancer (since studies show that women with this disease who are socially isolated have worse clinical outcomes)
  • Investigate a molecular mechanism (a tumor-suppressor gene called PTEN that is often inactivated in cancer) by which the social environment influences breast initiation and progression
  • Obtain breast tissue for use in this study from women undergoing biopsy for possible breast cancer at Ohio State’s Stefanie Spielman Comprehensive Breast Center
  • Use study findings to reveal potential diagnostic, therapeutic and prognostic tools for breast cancer and treatment

Clinical Trials for Breast Cancer

(OSU-13093) A Randomized, Multicenter, Open-Label, Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy for Patients With HER2-Positive Primary Breast Cancer Who Have Residual Tumor Present Pathologically in the Breast or Axillary Lymph Nodes Following Preoperative Therapy
NCT01772472
PI: William Farrar, MD
Objectives:

  • Evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor present in the breast or axillary lymph nodes following preoperative therapy
  • Randomize eligible patients to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every three weeks for 14 cycles
  • Provide radiotherapy and/or hormone therapy in addition if indicated

(OSU-10152) Phase 1 Study of IMC-CS4, a Monoclonal Antibody Targeted to the CSF-1 Receptor (CSF-1R), in Subjects with Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy is Available
NCT01346358
Objectives:

  • Establish the safety profile and characterize the pharmacokinetic profile of IMC-CS4 in treating subjects with advanced solid tumors that are refractory to standard therapy or for which no standard therapy is available
  • Weekly intravenous escalating doses of IMC-CS4

(OSU-13150) A Randomized Phase II Study of Trastuzumab Emtansine (T-DM1) vs. Paclitaxel in Combination with Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT Trial)
NCT01853748
Objectives:

  • Determine whether the experimental drug T-DM1 will result in fewer side effects than traditional HER2-positive breast cancer treatment involving trastuzumab and paclitaxel
  • Learn about the long-term benefits and disease-free survival of participants who take the study drug T-DM1 in comparison to those who take the combination of trastuzumab and paclitaxel

Recent Clinical Research Accomplishments

Novel Drug Combination Shows Benefit in Treating Metastatic Breast Cancer. OSUCCC – James researchers found in a phase II study that combining the drugs bevacizumab, trastuzumab and docetaxel is well tolerated and clinically active in patients with HER2-positive metastatic breast cancer. Bevacizumab is an agent that inhibits Vascular Epithelial Growth Factor (VEGF), a hormone that promotes formation of blood vessels that can sustain tumors. Patients in this study received the three drugs every three weeks for six cycles and then were allowed to receive bevacizumab and trastuzumab alone. Researchers say half of the 26 patients completed all six cycles of the three-drug combination and went on to receive the second combination. Their median progression-free survival was 14.3 months. Researchers contend that identification of predictive biomarkers should be included in further investigation of anti-VEGF therapy in breast cancer. Bhuvaneswari Ramaswamy, MD, was corresponding author on the study, which was published in the journal Investigational New Drugs.

Yoga Can Help Breast Cancer Survivors, Study Shows. Practicing yoga for as little as three months can reduce fatigue and lower inflammation in breast cancer survivors, according to a study at the OSUCCC – James. At the study’s six-month point—three months after the formal yoga practice had ended—fatigue was 57 percent lower, on average, in women who had practiced yoga compared with women in the non-yoga group, and inflammation was reduced by up to 20 percent among women in the yoga group. This was the largest known randomized, controlled trial that included biological measures, says first author Janice Kiecolt-Glaser, PhD. She said the study results could apply to other groups who have issues with fatigue and inflammation, but her team focused on breast cancer survivors because of the rigors of treatment. The study was published in the Journal of Clinical Oncology.

Ohio State Tests New Spice Derivation Formulation for Breast Cancer Prevention. A clinical trial at the OSUCCC – James investigates whether a new formulation of curcumin, a component of the spice turmeric, can reduce chronic inflammation that is thought to contribute to breast cancer. Principal investigator Lisa Yee, MD, says investigators are concerned that low-grade chronic inflammation puts certain women at increased risk for breast cancer. “We know that curcumin has potent anti-inflammatory properties,” she says. “The challenge is that it is minimally absorbed when eaten or taken as a pill, making it difficult to gauge its true potential as a cancer-prevention agent.” But the new oral curcumin formulation, called “nanoemulsion curcumin,” is designed to increase curcumin absorption in the body.

Translational Research Accomplishments

Study Shows How Stress Gene Enables Cancer to Spread. In an unexpected finding, scientists at the OSUCCC – James linked the activation of a stress gene called ATF3 in immune-system cells to the spread of breast cancer to other parts of the body. Researchers say this gene may be the crucial link between stress and cancer, including the major cause of cancer death—its spread, or metastasis. Previous studies have shown that stress is a risk factor for cancer, and researchers already knew that ATF3 is activated in response to stressful conditions in all types of cells. This research suggests that cancer cells somehow coax immune-system cells that have been recruited to the site of a tumor to express ATF3. Though it’s still unclear how, ATF3 prompts the immune cells to act erratically and give cancer an escape route from a tumor to other areas of the body. Tsonwin Hai, PhD was senior author of the study, which was published in the Journal of Clinical Investigation.

Possible Therapy for Tamoxifen-Resistant Therapy Identified. Researchers at the OSUCCC – James discovered how tamoxifen-resistant breast-cancer cells grow and proliferate. Like a second door that opens after the first door closes, the preclinical study showed that a signaling pathway called hedgehog (Hhg) can promote the growth of breast-cancer cells after tamoxifen shuts down the pathway activated by the hormone estrogen. A second signaling pathway, called PI3K/AKT, is also involved. Activation of the Hhg pathway renders tamoxifen treatment ineffective and enables the tumor to resume its growth and progression. But researchers also found that an experimental agent known as vismodegib, which blocks the Hhg pathway, inhibits the growth of tamoxifen-resistant human breast tumors in an animal model and could be a therapeutic option in humans. The study was published in the journal Cancer Research. Sarmila Majumder, PhD, was principal investigator; Bhuvana Ramaswamy, MD, was first author.

Triple-Negative Breast Cancer Subtypes Identified Using microRNA. A large-scale study of triple-negative breast cancer by researchers at the OSUCCC – James and collaborators in Italy showed that small molecules called microRNA can be used to define subtypes of this aggressive and often fatal malignancy. The findings could lead to new screening methods, prognostic markers and targeted treatments for this disease. The treatment of women with triple-negative breast cancer is challenging because it can be very different genetically among patients, but researchers believe these microRNA signatures will offer new insights into the biology of the disease and perhaps lead to better treatments. Kay Huebner, PhD, was co-senior investigator. The study was published in the journal Public Library of Science (PLoS) ONE.

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