Oncologists and researchers are discovering that when it comes to treating breast cancer, "doing less does more" for patients. This approach kills the cancer while improving cure rates and decreasing the chance of the cancer returning. It also spares patients the damaging side effects of treatment caused by toxic chemotherapy, less-precise radiation therapy, unnecessary diagnostic radiology and surgery.
Following is a summary of "less-is-more" trends in four areas -- drug therapy, radiation therapy, surgery and radiology -- from the perspective of breast cancer specialists at Seattle Cancer Care Alliance (SCCA), a specialty, academic-based treatment center that offers the latest clinical trials and customized treatment approaches for a wide variety of cancers.
Spare the chemo but not the cancer: Ten years ago, oncologists recommended chemotherapy for all women with early-stage breast cancer. Today, thanks to genomic testing of breast tumors to determine their receptivity or resistance to treatment, up to 50 percent of women can forego traditional chemotherapy for a less toxic alternative called targeted drug therapy.
For example, 80 percent of early-stage breast cancer is estrogen-receptor positive. This means that the cancer cells need estrogen to grow. Women with this type of breast cancer respond well to hormonal therapy that reduces or blocks the production or effects of estrogen. Such estrogen-blocking therapies often will work better than traditional chemotherapy, according to Julie Gralow, M.D., director of breast medical oncology at SCCA.
"Because chemotherapy is the most toxic of all the therapies, the fact that we can offer an effective alternative, hormonal therapy, is a very good thing for patients," Gralow said.
Side effects of chemotherapy include hair loss, substantial fatigue, increased risk of infections, and disruptions to family and work life. Some of these effects are short lived and most women will regain 80 to 90 percent of their energy level and function within a year, but for some women some side effects linger, such as reduced cognitive function (sometimes called "chemo brain") and early menopause. Hormonal therapy is not without its detriments, however, which can include menopause-related side effects such as osteoporosis, increased cholesterol levels and hot flashes. Estrogen-blocking therapy also takes longer -- a daily pill for five years versus three to six months of daily chemo infusions.
"Still, for most women, when you contrast hormonal therapy to chemo, it is night and day in terms of side effects," Gralow said.
Using PARP inhibitors to treat "triple negative" breast cancer: For the 15 to 18 percent of breast cancer patients who have so-called "triple negative" breast cancer -- tumors that don't respond to hormonal therapies such as tamoxifen or treatments that target HER2 receptors, such as Herceptin -- new hope is on the horizon. SCCA is a clinical trial site for a class of drugs called PARP inhibitors that can be used without chemotherapy for patients with triple-negative breast cancer who have also inherited a mutation called BRCA-1. Initial trials are in patients with metastatic disease, however, if proven successful, researchers can work to make the PARP inhibitors available for triple-negative, BRCA-1-positive patients with early-stage cancer, Gralow said.
Delaying chemo: Chemotherapy can be delayed significantly for some women whose cancer is discovered late, recurred or has spread to other parts of the body.
"Most breast cancer patients with metastatic or recurrent disease still must have chemotherapy at some point. However, with some new anti-estrogen and HER-2 agents under development, we've been able to push out the time patients can go before we need to start chemo -- and that can be several years," Gralow said.
These new drugs employ different biological pathways to attack tumors that have become resistant to initial anti-hormone therapies. SCCA is a clinical trials site for some of these therapies.
Spare the radiation treatment but not the cancer: Radiation oncologists at SCCA are working on two new methods for delivering less radiation to certain breast cancer patients, including one that may also spare the need for some women to undergo a mastectomy.
Janice Kim, M.D., a breast radiation oncologist, plans to lead a new treatment protocol at SCCA for women whose early-stage breast cancer recurs after undergoing lumpectomy and initial radiation therapy. Standard treatment for breast cancer recurrence is a mastectomy without radiation, because too much radiation can lead to permanent damage of normal tissues in the breast.
Instead, under the new approach, women will undergo a second lumpectomy followed by a technique called "accelerated partial breast irradiation." Oncologists already know from previous studies that doing a lumpectomy alone will not prevent the cancer from recurring a third time. The idea behind Kim's approach is to hit the "tumor bed" with high doses of radiation twice a day for only five days. If it works, the result is less surgery and radiation for the patient while still killing the cancer. Kim's study is funded by a grant from The Safeway Foundation.
Use a GPS-like tracking system to protect the heart during radiation therapy: To reduce radiation exposure to the heart during radiation therapy, breast cancer patients with tumors in the left breast can hold their breath while the beam is fired. This action moves the heart away from the chest wall, out of the radiation beam path. However, the breath-hold method must be precise to ensure that the heart is maximally protected.
Led by L. Christine Fang, M.D., the SCCA radiation oncology team developed a unique solution to this challenge: adapt a GPS-like tracking system utilized in prostate cancer treatment for use in women with left-sided breast cancer.
SCCA already uses the radio beacon transponder system, made by Seattle-based Calypso Medical, to monitor the position of the prostate to spare surrounding tissue from radiation exposure. Working with Calypso, the SCCA team developed a prototype surface transponder and about 35 breast cancer patients have successfully undergone radiation treatment using it. Unlike the prostate transponders -- each about the size of a long grain of rice, three of which must be directly implanted into the prostate -- the L-shaped device, comprised of two transponders encased in glass, sits on the skin surface. This new surface transponder has been approved by the U.S. Food and Drug Administration.
"The Calypso system has millimeter precision to provide continuous real-time monitoring of the breath-hold while the radiation beam is on," Fang said. Therapists instruct patients to achieve the right amount of breath intake and position during which to activate the radiation beam.
Currently, SCCA is one of three clinical cancer sites in the U.S. using the new surface transponder. Fang will be the principal investigator of a multi-institutional study using this system.
Spare the lymph nodes but not the cancer: Nearly all women diagnosed with breast cancer will require some kind of surgery to remove the tumor. How much surgery and what kind depends upon the type and extent of the cancer. Surgeons at dedicated, academic cancer treatment centers such as SCCA can offer a number of options for breast cancer patients including those that spare as much tissue as possible and maintain the shape and feel of the breast after a tumor has been removed.
For example, a landmark study published in 2010 resulted in a substantial change in how the lymph nodes are managed in breast cancer. Referred to as the Z11 trial, the study showed it isn't mandatory to remove all of the lymph nodes of women whose disease has spread to the armpit region. Before publication of the Z11 study, the first lymph nodes that communicate with the tumor, called the sentinel nodes, were tested for the presence of cancer cells. If even one of these sentinel nodes was positive for tumor cells, additional nodes in that area, called the axillary nodes, were removed in a procedure called an axillary lymph node dissection. The Z11 study, however, showed that patients with small tumors who underwent a lumpectomy and subsequent whole-breast radiation did not necessarily require the additional lymph node removal if only one or two of their sentinel nodes were positive for tumor cells. Despite a fear that nodes that harbored cancer cells would be left behind and cause problems, after following those patients for more than five years, the Z11 study demonstrated that they do just as well as those whose nodes were removed.
Removing fewer nodes means a significantly reduced risk of lymphedema, or swelling of the arm.
"Although lymphedema can be treated with physical therapy, it can remain a lifelong nuisance, if not a true medical issue, and result in scarring, injuries to the armpit structures and limited range of motion," said Kristine Calhoun, M.D., a breast surgeon at SCCA. "All of the breast cancer surgeons at SCCA have embraced the Z11 study and have adjusted their practice to apply this to patients where such management is appropriate."
Spare the nipple but not the cancer: For women undergoing mastectomy with reconstruction, surgery to spare the nipple has increased in use. Previously, such nipple-sparing practices had been used most often for women at high risk of breast cancer who chose to have one or both breasts removed as a preventive measure. Now some women with early-stage cancer whose tumors are located well away from the nipple also qualify for nipple-sparing surgery.
Spare the diagnostic radiation but not the cancer: "Image gently and image wisely are concepts born from the recognition that we want to focus on achieving the best patient outcomes while reducing any potential harm and keeping costs down," said Constance Lehman, M.D., Ph.D., director of radiology at SCCA and an international expert on the use of advanced imaging tools such as MRI and ultrasound.
For example, Lehman uses ultrasound instead of mammograms in women under 40 with palpable breast lumps to pinpoint possible tumors and guide biopsy decisions. This is because younger women have denser breast tissue, which makes tumors harder to detect by mammogram. Ultrasound uses non-ionizing radiation, which is less risky than ionizing radiation used in mammography. Ultrasound finds more tumors than mammography in this patient population, is a less costly exam and is more comfortable for patients.
Lehman also advocates for the use of magnetic resonance imaging, or MRI, in all women who've been diagnosed with breast cancer as well as those who are at high risk, because MRI will find significantly more cancers than other imaging methods.
Such advanced imaging tools also show promise for identifying women diagnosed with noninvasive cancer, such as ductal carcinoma in situ (DCIS), who can be treated with more individualized therapies. DCIS is an early stage breast cancer in which abnormal cells are confined to the milk ducts but have the potential to become invasive disease. As a result, all forms of DCIS currently are treated aggressively. SCCA radiologist Habib Rahbar, M.D., and his breast-imaging colleagues have identified promising uses of MRI that could help predict which DCIS lesions are likely to remain indolent and do not warrant radiation or even surgical therapies.
"We hope to eventually reduce unnecessary DCIS treatments by combining MRI features with clinical and pathology information," said Rahbar, who is currently completing a prospective DCIS imaging trial funded by a pilot grant from The Safeway Foundation.
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