SABCS: Genetic Testing, Radiation Treatment, and Treating Lymphedema

 

San Antonio Breast Cancer Symposium—Day 1

December 8, 2010

By Jane Zones, BCA Board Member

Before SABCS has its official welcoming Thursday morning, there are a series of educational meetings for physicians and advocates covering a range of basic topics of interest to women living with breast cancer.   The talks Wednesday, sponsored by the Susan Komen Foundation, are more easily understood and of broader scope than the very focused research reports that begin Thursday.

Genetic Testing

Sharon Plon, MD (Baylor) described family-based genetic sequencing, which identifies the specific mutation or mutations in a person who has breast cancer, so that subsequent testing of a family member who may be at higher risk will hone in on that particular variant.  If the cancer patient tests negative, or if variants of uncertain significance (VUS) are found, there is no testing of relatives.  This is a more efficient and less costly way to determine whether relatives have inherited risk than to assess their whole genetic sequence.

Plon and her colleagues, who are geneticists, surveyed a broad range of physicians who were in specialties likely to prescribe testing—family practice, internal medicine, Ob-Gyn, general surgery, and hematology/oncology.   They presented a hypothetical case, involving sisters in their 40’s—and asked the doctors what they would recommend.   Most prescribed comprehensive testing rather than focus on the specific genetic variant of the relative with cancer, and though the majority understood that finding a VUS did not require further testing of relatives, they recommended follow-up testing anyway.  The researchers estimated that the cost of conducting the narrower test was $950, compared to the $10,000 estimated median cost of the testing decisions of those surveyed.

Plon suggested that doctors specify the exact nature of the mutation found in a letter to patients when they inform them of their results, as well as its implications for their health care.  This letter can then be used by relatives who may seek testing from their own providers.

The researchers also recommend utilizing a classification system that assesses the level of pathogenicity of the genetic variant to guide them in decisions about further testing.

Other talks in this session included one on management of BRCA1/2 mutation carriers (oopherectomy to reduce risk was recommended for women at age 40, and prophylactic mastectomy for women at age 25), and another on non-BRCA mutations that increase risk of breast cancer (these others occur with greater frequency than BRCA1/2, but have a much lower relative risk of breast cancer).

Radiation Techniques

The moderator of this session practices at the large academic health center in San Antonio, which he pointed out is the shotgun capital of the United States.   He showed a slide of himself with three colleagues in skeet shooting gear, all with shotguns, and his talk presented an overview of various radiotherapy equipment and how well it targets tumors without exposing healthy tissue to radiation.  This was the gun show portion of the session.

The other speaker, Frank Vicini, reviewed research on partial breast radiation (PBR) in comparison with whole breast radiation, as well as the advantages of shortening the duration of radiotherapy using increased dosage.  Accelerated radiation treatment may be completed in 4 to 5 days after surgery, compared to the conventional 6 to 7 weeks.  This is particularly significant for patients who do not live near radiation treatment centers. While the studies reviewed showed comparable results for both these innovations, they are not of long enough duration to assess long-term toxicity.

Dr. Vicini urged his audience to support patient enrollment in the NSABP (National Surgical Adjuvant Breast and Bowel Project) Phase III trial of accelerated partial breast irradiation (APBI), which has been ongoing since 2005.  [Remember NSABP?  This decades-long series of NCI-sponsored trials showed us that breast conserving therapy was as safe and effective as mastectomy and that tamoxifen lowered breast cancer risk in healthy women—but caused so much cardiovascular disease that it never became widely used by women without breast cancer].   Enrollment in the APBI trial has been slower than anticipated, and will close in 2012.  Researchers are hoping to increase the current level of participation (around 4300 now) so that they can establish firmer results and longer-term outcomes than the much smaller trials that have been reported to date.

Symptom Management

The session on managing side effects of breast cancer treatment was moderated by UCSF’s Laura Esserman.  This included very interesting and potentially useful information on lymphedema, herbal treatments, managing chronic pain, and preventing hair loss during chemotherapy.

Weight Training and Lymphedema

All presenters at SABCS are required to disclose any conflicts of interest they may have related to what they are reporting.   Kathryn Schmitz, who does research on lymphedema at the University of Pennsylvania, had a disclosure slide that stated “I WISH.”  She complained that there was little commercial (or academic) interest in the topic.

Although everyone “knows” that women who have undergone mastectomy should avoid vigorous exercise or lifting heavy objects to reduce the risk of swelling of the arm from lymph fluid drainage, Dr. Schmitz found that this widely known and practiced maxim was not evidence-based, and she set out to look into it.

There are many reasons to be concerned about lyphedema.  An estimated 35 to 58% of women who have had mastectomies have arm or shoulder issues, mostly lymphedema or rotator cuff problems.   This is particularly difficult for women for whom physical labor is a necessary part of their employment.  Furthermore, regular physical exercise is associated with reduced risk of recurrence, and it is nearly impossible to do lower body exercise without involving the upper body.  Breast surgery and radiation exacerbate pre-existing upper body difficulties.

Meanwhile, breast cancer treatment reduces the ability of the lymph system to respond well to infection, injury, trauma, and inflammation, all of which are improved with exercise.  The lymphatic system transports about two liters of fluid daily, a liquid that is heavy with protein and fat molecules.

Because little is known about the relationship between exercise and lymphedema, Schmitz and her colleagues began the Physical Activity and Lymphedema (PAL) trial, a one year randomized clinical trial, results of which were published on-line in JAMA at the very time she was giving this talk.   PAL randomized 140 women with lymphedema into a treatment or a control group, and did the same with 150 women without lymphedema (all had been cancer patients).  Over a third of the participants were Black women.

Schmitz and colleagues hypothesized that a rehabilitation model of strength training (“supervised slowly progressive controlled increase in physiological stress”) would be preferable to leaving women to go out “into the wild”—confronting acute physical stress just in the activities encountered in daily life.

The treatment group received twice-weekly training sessions for thirteen weeks, while controls were provided no incentives to exercise.  At the end of the year-long experiment, the women in the exercise group were not only much stronger, but had half as many flare-ups of lymphedema as those in the control group.  These findings were true for both those who entered the study with lymphedema, and those who were at risk for developing lymphedema.  The researchers concluded that supervised, slowly progressive strength training was not only safe for women with lymphedema, but it had many benefits as well.

Preventing Hair Loss During Chemotherapy

Hair loss during chemotherapy is traumatic for many women, and causes some (as many as 8%) to refuse treatment. Michelle Melisco, a UCSF physician and researcher, reported on a study, “Hair to Stay,” that is looking at the feasibility of chemotherapy patients using a “cold cap” during treatment in order to preserve their hair.  Cooling the scalp to very low temperatures causes vasoconstriction, which reduces biochemical activity and minimizes chemical action on the hair follicles.

There are a variety of caps that are used internationally, mostly outside the US, but not much solid research about their feasibility or effectiveness.  More recent studies have found more positive results, perhaps reflecting improved technology, or possibly a result of commercial bias in study design and conduct.

Melisco (who has a head of abundant long hair) described various types of cold caps and  cooling systems, none of which is approved as yet by the FDA, but which utilize approved ingredients in their manufacture.   One of the caps is composed of a silicone shell which contains fluids that are used to maintain freezing temperatures while allowing the cap to be molded over the head.  Multiple caps are used during the chemo infusion,  changed as they gain warmth before, during and after treatment, and they can be rented.   (The Rapunzel Project–http://www.rapunzelproject.org/–has lots of information about the products and procedures).  A special freezer that can maintain very low temperatures is used to freeze the caps.   Dry ice is an alternative coolant, but much less convenient to use.

Previous studies have shown that women who adhere to scalp cooling are more likely to preserve their hair (success rates vary), and those who keep their hair are quite satisfied with the process.  However, those who use scalp cooling and still lose their hair are more unhappy than those who lose their hair without being treated with the cooling system.  One disturbing side effect is increased likelihood of scalp metastases (<2.5%).

The UCSF study is a Phase One trial to determine the feasibility of cold cap use.   If more than half of “Hair to Stay” participants discontinue use during the course of chemotherapy, the researchers intend to stop the study.  If enough subjects complete the regimen, Melisco and her colleagues will approach the FDA to get approval for a Phase Two trial that focuses on the effectiveness of the treatment.  Meanwhile, they are assessing a variety of secondary endpoints, including types of chemotherapies and, of course, a systematic measure of hair loss.

Melisco is hoping to demonstrate enough success to win FDA approval for the method, which would make it potentially reimbursable by insurers.