Physician-scientists at the Johns Hopkins Kimmel Cancer Center are helping set the standard of care for breast cancer therapies, says Dr. Vered Stearns, co-director of the Breast Cancer Program. Clinicians are always researching new therapies or new combinations of existing therapies to maximize each patient’s response to treatment.
“We are embarking on a new era of cancer management as treatment is becoming more tailored to the individual patient’s genetic makeup,” says Dr. Stearns, an internationally recognized breast cancer researcher. Dr. Stearns’ work using biomarkers to guide breast cancer prevention and treatment strategies, and deciphering genetically determined variations in patients’ responses to the breast cancer drug tamoxifen, has earned widespread recognition. Her work also led to improved therapeutic options for women suffering from hot flashes.
Dr. Leisha Emens specializes in breast cancer vaccine clinical trials that teach the dendritic cells to recognize that tumor cells are different from normal cells and thus need to be attacked and destroyed. Using the vaccine in combination with
chemotherapy enhances the vaccine’s ability to excite the immune system against cancer.
Treatment Philosophy: Tailored Therapies
Before determining a course of treatment, oncologists here try to determine the subtype of breast cancer to tailor therapy. They will take a breast tissue sample for examination through biopsy or surgery; samples usually are reviewed by Hopkins’ pathology department. The oncologists will look to see if the tumors express estrogen (ER) or progesterone (PgR) receptors, or human epidermal growth factor receptor 2 (HER2). They also will consider the proliferation index, a measure of how many times cancerous cells have divided. These criteria help determine the category of treatment(s) recommended.
If the cancers are found to express estrogen or progesterone receptors, or HER2, patients are likely to be referred for hormone therapies such as tamoxifen. If they do not test positive for those hormone receptors, they likely will be referred for chemotherapy. Hopkins oncologists also may use a more sophisticated molecular test for early-stage cancers that express the estrogen receptor. The test looks at 21 genes to determine whether a particular tumor will respond to hormone therapy alone or if chemotherapy will also be needed.
For early-stage cancers, the most common medications include anthracyclines such as doxorubicin, or taxanes like paclitaxel or docetaxel. More advanced cancers are prescribed other treatments.
Metastatic cancers are treated based on their subtype. Those that express the estrogen receptor may be treated with hormone therapies and then chemotherapy. Our oncologists also are pursuing research in new agents to reverse resistance to treatment. For women who do not express ER, PgR or HER2, the main treatment is chemotherapy-based, or not-yet approved targeted agents being studied in clinical trials.
“We try to have a clinical trial for everyone,” says Dr. Stearns. “Every step of the way there’s room for improvement.”
If a patient already has been through first- and second-line therapies and the cancer has progressed, Dr. Stearns says she and her colleagues try to encourage participation in clinical trials. Our oncologists will help patients sort out which trial may be best for them.
Other options, depending on where the cancer is, the number of prior treatments and the sites on the body, include radiofrequency ablation, radiation and surgery. In radiofrequency ablation, a needle-like probe is placed inside the tumor. A high-frequency alternating current passing through the probe increases the temperature within tumor tissue that results in destruction of the tumor.
A Vision for Personalized Medicine
In her new role as co-director of the Breast Cancer Program, Dr. Stearns says she will focus on the emerging era of cancer management in which treatment is tailored to the unique genetic alterations contained within each individual patient’s cancer.
With the genetic and epigenetic discoveries made at the Kimmel Cancer Center during the last several years, including the mapping of the breast cancer genome, Dr. Stearns and her collaborators hope to personalize preventive and therapeutic strategies for patients. In the past, cancer was a general name for a group of hundreds of diseases. Based on the new genetic understanding of cancer pioneered at our center, it may actually be closer to 500 diseases; breast cancer alone is recognized as six distinct diseases, with more likely to emerge.
“Within the next few years, all cancer patients at the Kimmel Cancer Center will have their tumors analyzed to reveal a unique ‘fingerprint’ representing a specific combination of genetic and epigenetic alterations,” Dr. Stearns says. “This will change the way we study new drugs and use old ones. Instead of trying them on all breast cancer patients, we can direct them to the patients whose cancers contain the specific gene change targeted by the drugs, ensuring that the best treatments get to the right patients.”
Setting the Standards of Care
Dr. Stearns has been instrumental in building a translational research team and the infrastructure for implementing innovative early clinical trials. The program is home to experts in the fields of hormone resistance, epigenetic regulation and biomarkers, metastasis and immunotherapy.
The Kimmel Cancer Center is one of few cancer centers in the country setting the standard of care for breast cancer therapy and for survivors following treatment, says Stearns: “We excel in giving patients the best possible care from the very beginning of and throughout their cancer journey.”
As continued research leads to improved treatments, there will be a greater number of breast cancer survivors. Dr. Stearns is interested in expanding the clinical management of side effects, including those that affect women long-term, such as premature menopause and toxicities related to prior chemotherapy use.
Even in her personal work, Dr. Stearns allocates a significant amount of time to investigating new treatments and approaches to ameliorate hot flashes and other symptoms commonly experienced by breast cancer patients. Incorporating basic, clinical, and population science, her team’s research has answered fundamental questions about the mechanisms of breast cancer at the molecular level and led to new interventions.
Matching Breast Cancer Patients With the Right Drug
Groundbreaking discoveries led by Johns Hopkins Kimmel Cancer Center scientists in the 1990s determined that cancer occurs as a result of a cascading series of cellular alterations --- dramatically changing the way we look at cancer therapies. With advanced technologies, scientists now can pinpoint different types of cancers within a disease group. Breast cancer, for example, is now considered as several diseases that look alike under a microscope but genetically are very different, says breast cancer expert Antonio Wolff, MD. This is why two women with seemingly similar breast cancers respond quite differently to treatment.
Long before ‘personalized medicine’ became a medical buzzword, physician-scientists at the Johns Hopkins Kimmel Cancer Center used personalized approaches to determine the most effective therapy for breast cancer patients. In the late 1980s, scientists identified the HER2 gene, finding that women with increased levels of HER2, as detected by tests that measure the number of copies of the HER2 gene or the amount of its protein in breast cancer cells, often have more aggressive tumors. Scientists also follow the receptors for estrogen and progesterone that found in two-thirds of all invasive breast cancers.
“There is clearly a need to accurately identify breast cancer subtypes as they are critical to help doctors and their patients individualize treatment decisions,” Dr. Wolff says.
Dr. Wolff Directs New National Screening Guidelines
Dr. Wolff served as co-chair of a national panel of oncologists and pathologists that released new practice guidelines in 2010 recommending that all patients with invasive breast cancers and breast cancer recurrences be tested for estrogen receptor and progesterone receptor status, and that those tests be considered positive if as little as 1 percent of the tumor cells test positive.
Overall, about 65 percent of breast cancers are ER-positive, 15 percent to 20 percent are positive for human epidermal growth factor 2 (HER2), and 15 percent are “triple negative,” meaning they lack receptors for estrogen, progesterone and HER2. The guideline, released through the American Society of Clinical Oncology and the College of American Pathologists, aims to improve the accuracy of test results and ensure all patients receive appropriate care for their specific breast cancer subtype. Endocrine treatments can substantially improve survival in patients with hormone receptor-positive invasive breast cancer.
“Our main goal was to improve the accuracy of predictive biomarker testing in everyday practice and ensure that patients receive the right treatment for their specific breast cancer subtypes to maximize their chances of surviving breast cancer,” Dr. Wolff says. “Widespread access to high-quality routine pathology assessment and accurate testing for ER, PR and HER2 is a critical issue worldwide.”