Breast Cancer: Advances in Diagnosis & Treatment
BY GWENDOLYN STRITTER, MD
INTRODUCTION
The past year has seen significant forward movement in the breast cancer
field. It is very exciting to see high-quality research on alternative
medicine techniques as well as allopathic (conventional) ones.
Currently, chemotherapy is a vital part
of allopathic breast cancer treatment, for both primary and metastatic
disease. As advances in chemotherapy are thoroughly covered in other
publications, I will instead focus on non-chemotherapy advances in this
article.
This
year, I have seen new research giving us more information about which
herbs, supplements, and other alternative/complementary approaches can
minimize treatment side effects and possibly even reduce the risk of
breast cancer recurrence. Other progress has improved our ability to
determine the full extent of a primary breast cancer, making possible
better surgical planning. Finally, I have seen broader acceptance of
tests allowing women less likely to benefit from chemotherapy to forgo
it with confidence.
ANTIOXIDANTS & CHEMOTHERAPY
An excellent article by Dr. Keith Block reviewed 845 studies, discarding
all those that were not randomized or controlled.1 The remaining 19
studies showed that antioxidants such as glutathione, melatonin, vitamin
A, vitamin E, vitamin C, ellagic acid (from raspberries, strawberries,
and cranberries), and N-acetyl cysteine did not adversely affect the
outcome of patients who were also on chemotherapy. In fact, these patients
had improvements in their survival time, tumor responses, or both.
As
more highquality studies are published, I hope to see more oncologists
using antioxidants with chemotherapy.
BOSWELLIA USE IN BRAIN METASTASES
Last year, Dr. Dana Flavin at the Foundation for Collaborative Medicine
and Research in Greenwich, CT, reported on a remarkable case of a woman
with breast cancer whose multiple brain metastases showed no improvement
after two weeks of Xeloda and brain radiation.2 She was then started
on boswellia 800 mg three times a day. (Boswellia, also known as Indian
frankincense, is an herbal supplement with anti-inflammatory properties
and is generally available through retail and online health food stores.)
Ten weeks later, a repeat brain CT showed complete resolution of the
brain metastases. Impressively, she has been maintained on boswellia
for the past four years with no recurrent brain metastasis.
Subsequently, Dr. Flavin has had two more
women with brain metastases greatly improve using the same regimen. Reportedly,
Harvard's
Dana Farber Cancer Center is seeking approval for a clinical trial to
study boswellia use in this setting.
NUTRITION CONTROVERSIES
The December 2006 San Antonio Breast Cancer Symposium (SABCS) saw the
unveiling of the Women's Intervention Nutrition
Study (WINS), a large randomized, controlled trial that compared breast
cancer patients on high-fat and low-fat diets.3 This study was a joint
effort by several institutions including Beth Israel Deaconess Hospital,
Memorial Sloan-Kettering Cancer Center, and the University of California,
Los Angeles. They found a substantial survival benefit in the low-fat
group, especially for those with estrogen receptor-negative cancer.
In contrast, the Women's
Healthy Eating and Living (WHEL) study published recently by the University
of California at San Diego showed no survival advantage of a high vegetable/fruit,
low-fat, and high-fiber diet.4 Although this trial was also large, randomized,
and controlled, it had two key differences from WINS: first, the low-fat
group in the WHEL study had, on average, a much higher daily fat intake
than those in WINS (45 grams versus 33 grams). Second, the women in the
WHEL study gained weight as opposed to those in WINS who shed pounds.
Since a Mayo Clinic study showed that breast cancer survivors who gain
weight have reduced survival, it is quite possible that whatever benefit
the WHEL participants derived from the relatively low-fat and high vegetable/fruit
intake was neutralized by their weight gain.5
Interestingly, the same group who published the WHEL study joined Stanford,
the Northern California Kaiser Permanente group, and others in a large
multi-institutional clinical trial. They found that when women
with breast cancer combine higher vegetable-fruit consumption with increased
physical activity, their chances of surviving increased by nearly 50%,
regardless of their level of obesity.6
PSYCHOSPIRITUAL ASPECT OF BREAST CANCER
An interesting study out of Baylor College of Medicine noted that women
who blamed themselves for their breast cancer and lacked self-forgiveness
reported more mood disturbances and a lower quality of life.7
Another report in the Journal of the National
Cancer Institute showed that breast cancer survivors, particularly African-Americans,
have a higher rate of suicide than the rest of the population.8
These
studies point to the importance of psychological health and reinforce
the fact that a proactive approach to emotional issues is a key part
of an integrative breast cancer treatment program.
ALTERNATIVE APPROACHES
There are various alternative approaches that have shown to be beneficial
in recent studies:
» Aromatherapy massage was shown to reduce anxiety and depression.9
» Yoga improved sleep, physical function, and possibly also fatigue in
women getting radiation therapy.10
» Reiki, an energy-based healing system from Japan, improved fatigue
in cancer patients.11
» Mayo Clinic research suggests that American ginseng at 1000 to 2000
mg per day may be effective for alleviating cancer-related fatigue.12
» A Columbia University study showed that acupuncture can reduce the
joint pains caused by aromatase inhibitors such as Femara and Arimidex.13
» Eight weeks of aerobic exercise was shown to improve depression and
fatigue as well as improve physical conditioning in breast cancer survivors.14
» I
was intrigued by Duke University's report that women taking
calcium supplements had more hot flashes that those who did not. This
small study was presented at the ACSO Breast Cancer Symposium two
weeks ago. It remains to be seen whether this relationship
holds up under larger, more rigorous studies.15
BREAST MRI
Breast MRI continues to be an area of active research. It is well documented
that up to 15% of breast cancers are missed by mammogram and breast
ultrasound.16 MRI will catch most of these.
Despite this obvious
advantage, MRI is not yet ready to replace mammography as our standard
screening tool as it does have a significant false-positive rate. In
other words, it is very good at finding even tiny breast lumps, but it
cannot always distinguish a benign lump from a malignant one.
Nevertheless, one group of women were
found to be excellent candidates for MRI breast screening: those with
a high risk of developing breast cancer within five years. Women with
BRCA gene mutations fall into this category. In addition, women who have
a 20% or greater lifetime risk of breast cancer also fall into this group.
One easy way to estimate one's risk is to use the Gail
risk model, an interactive computer program where inputting specific
information such as age and family history of breast cancer yields an
estimate of both 5-year and lifetime risk of breast cancer. It can be
accessed at the National Cancer Institute website: www.cancer.gov/bcrisktool.
For those who have already been diagnosed with breast cancer, a breast
MRI can add to the information provided by the mammogram to help plan
a surgery that will be sure to remove all of the cancer. In fact, researchers
have shown that in at least 16% of women, a preoperative MRI found a
second cancer that the mammogram had missed and that would probably have
escaped the planned lumpectomy.17 In another study, MRI findings resulted
in a change in surgical plans in 15% to 30% of cases.18,19
Additionally, a small study from New York University was just presented
at the ASCO Breast Cancer Symposium, showing that women who had preoperative
MRI not only tended to have a lower rate of re-excision and improved
surgical margins, but also had fewer mastectomies.20 I am now beginning
to see breast surgeons who routinely incorporate MRI in their pre-operative
protocol.
Unfortunately, this research is not mature enough to say definitively
whether preoperative breast MRI is beneficial. In the meantime,
those women who would rather risk a negative (i.e. unnecessary) biopsy
than a potentially incompletely excised cancer should talk to their breast
surgeons about an MRI.
It is important to note that there are
currently no national standards for breast MRI imaging as there are for
mammograms. Therefore, it makes sense to have your MRI done at a center
that uses dedicated breast MRI coils and whose radiologists have at least
three years of experience interpreting them.
GENE EXPRESSION PROFILING
I am very happy to report steady advances in the realm of personalized
treatment. For many years, women with lymph node-negative, early stage
breast cancer were encouraged to undergo chemotherapy even though only
2% of those over 50 years of age, and only 7% of those under 50, would
be expected to benefit from it.21 (Although the percentage of women
with early stage breast cancer being saved by chemotherapy seems small,
when multiplied by the hundreds of thousands of women diagnosed, it
actually translates into thousands more women surviving their breast
cancer each year.) The problem is that you have to give chemotherapy
to many, many women in order to save one. For example, for every
100 women over 50 being treated, 98 would get chemotherapy, with all
its side effects but none of its benefit, in order to save two women.
This situation changed dramatically in 2003 when
a company called Genomic Health burst on the scene with an elegant test
to help decide who would benefit from chemotherapy. They examined DNA
from thousands of breast cancer samples from women whose ultimate response
(relapse or no relapse) to tamoxifen was known. They found 21 genes that
accurately predicted whether a woman with hormone-positive breast cancer
taking anti-estrogen therapy would relapse over the next 10 years. The
result is OncoType DX, a gene expression profiling test that has now
allowed many women to forgo chemotherapy with confidence.
Agendia is another biotech company whose gene profiling test was approved
by the FDA this year. Called MammaPrint, it uses a 70-gene profile and
has been shown to be as accurate as the Oncotype DX test in predicting
breast cancer relapse.
There are
differences between the two tests. Oncotype DX requires the breast cancer
be lymph node-negative, early stage, and hormone receptor-positive. It
can use preserved breast cancer specimens, so even if the cancer was
removed years ago, the test can still be done on that tissue sample (pathologists
always save tissue specimens). The MammaPrint test requires women to
be early stage and lymph node-negative but does not require them to be
hormone receptor-positive. However, it does require a fresh tissue sample
taken at the time of surgery.
Surprisingly, many oncologists still choose not to discuss these exciting
new tests with their patients.
TUMOR MARKERS
A blood test that accurately tracks metastatic cancer activity is a holy
grail of sorts in the breast cancer diagnostic world. Armed with the
results of this test, one can monitor the effectiveness of the current
treatment regimen more quickly. Such a test, called a tumor marker, certainly
has advantages over CT, MRI, and PET scans in that it can be done more
frequently and without exposure to radiation.
For many years, the only choices were blood tests for CA 15.3 or CA
27.29. Unfortunately, these tumor markers were useful only for some women.
Recently, a new blood test has become available that
looks for cancer cells, called circulating tumor cells, in the bloodstream.
This test, called Cell Search, uses monoclonal antibodies to find as
few as one cancer cell per billion normal cells in a small sample of
blood.22 The FDA has approved this test only for women with metastatic
breast cancer. It is available from Quest Diagnostics and many other
laboratories.
Women with metastatic HER2-positive breast
cancer now also have a more accurate tumor marker. Monitoring the HER-2
ECD blood test over time has proved very useful in this regard as noted
by several research papers presented at the San Antonio Breast Cancer
Symposium (SABCS) and the American Society for Clinical Oncology annual
conference (ASCO).23,24 This FDA approved test may be obtained through
Specialty Laboratories.
CELEBREX FOR METASTATIC BREAST CANCER
Last year, a group of French researchers published the results of a well-designed
study looking at a new drug combination for treating breast cancer.25
They used Celebrex, a COX-2 inhibiting anti-inflammatory medication,
and Aromasin, an anti-estrogen drug. This combination was prescribed
as the first-line treatment for metastatic breast cancer and was compared
to using Aromasin alone. The Celebrex plus Aromasin group had 75% more
women whose cancer went into complete or partial remission than did
those who took Aromasin alone.
Interestingly, women who took Celebrex
plus Aromasin had significantly less pain, joint aches, fatigue, and
insomnia. But more of these women experienced edema (about 8% versus
2% in the Aromasin alone group) and hypersensitivity reactions. In fact,
anyone who is allergic to Sulfa should not take Celebrex, but should
take another COX-2 inhibiting anti-inflammatory agent instead.
Although
this study was done with Aromasin, other aromatase-inhibiting anti-estrogens
such as Femara and Arimidex may very well work with Celebrex in the same
way.
ER-NEGATIVE BREAST CANCER MAY RESPOND TO ANTI-ESTROGEN THERAPY AFTER
ALL
At the December San Antonio Breast Cancer Symposium, much excitement
surrounded a multinational study of the effect of aromatase inhibitors
on estrogen receptor-negative breast cancer.26 In short, they tested
the truism that estrogen receptor-negative cancers do not respond
to anti-estrogen therapy.
This elegant study gathered
the initial breast cancer samples of 116 women and noted their estrogen
receptor status. Some had their cancers progress and, despite being estrogen-negative,
were treated with aromatase-inhibiting anti-estrogens. It turned out
that a notable 18% of these women had their cancer shrink when they took
either Femara or Arimidex.
These results may mean that currently
accepted methods do not always detect estrogen receptor-positivity accurately
enough. In fact, recent research shows that looking for estrogen-related
genes is a much more accurate way of determining estrogen receptor status
than the current standard that relies on estrogen receptor dyes.27
The bottom line: when a post-menopausal estrogen receptor-negative cancer
is resistant to standard treatment, it makes sense to consider trying
Femara or Arimidex.
HER-2 POSITIVE METASTATIC BREAST CANCER
A recent flurry of studies have shown that women whose cancers grew while
on Herceptin but continued the Herceptin treatment anyway, lived up to
twice as long as those who did not.28,29,30,31
CURRENT HER-2 TESTING PROTOCOLS MAY BE INADEQUATE
A well-respected breast cancer research group called the National Surgical
Adjuvant Breast and Bowel Project caused a stir at the ASCO meeting
this year. They showed that the IHC and FISH protocols currently used
for determining HER-2 status do not predict which women will
respond to Herceptin.32 In fact, women who were IHC 2+ or less, or
who were FISH-negative but received Herceptin anyway, had a 50% to
80% lower breast cancer recurrence rate than those who did not receive
it.
Of course, the top
researchers in the breast cancer treatment world, including the authors
of this study, hastened to say that this is a preliminary study and oncologists
should not be giving Herceptin to women unless they are FISH-positive
or IHC 3+ positive for HER-2. While this may be sound public health policy,
in an individual case that is resistant to standard treatment, it makes
sense to consider trying Herceptin if it has not been tried yet.
In a related study, Italian researchers gave Herceptin
to women whose cancers were HER-2 negative according to the standard
protocol but were found to have the HER-2 protein in their blood (according
to the serum HER ECD blood test).33 These women had more cancer shrinkage
when given Herceptin than those who did not receive Herceptin.
HELP FOR "CHEMOBRAIN"
Provigil improved memory and attention in a randomized, controlled trial
of women who had chemotherapy for their breast cancer. Of note, scientists
from Cephalon, the pharmaceutical company that manufactures Provigil,
participated in this study.34
ON THE HORIZON
I am optimistic about the continued advancement of cancer vaccines. The
underlying science has been more difficult to conquer than many had
envisioned. Nevertheless, the latest round of vaccines in clinical trials
has shown some promise.
Vaccines for HER-2 Positive
Breast Cancer
Every year sees more anti-HER-2 vaccines introduced into clinical trials.
Currently, there are at least five such vaccines being tested. A particularly
promising one, E75, was given to women who were at high risk for cancer
relapse after receiving the standard treatment.35 There were about 60%
fewer relapses at two years compared with those who did not receive E75.
A Phase III trial is currently in the planning stage.
Vaccines for Metastatic Breast Cancer (HER-2 Positive and Negative)
The
National Cancer Institute presented its latest data on PANVAC at the
ASCO Breast Cancer Symposium. PANVAC
is a fascinating vaccine that uses a virus to deliver potent immune-activating
substances directly to the cancer site. It is hoped that PANVAC
will mobilize the immune system to seek out and destroy every breast
cancer cell in a woman's
body. While it showed some activity when used as a single agent,
the recent NCI study using it in combination with the chemotherapy agent
Taxotere showed promising prolonged partial remissions in the two patients
who have tried it so far.37
Crying for Better Breast Cancer Screening
The most paradigm-shifting
research presented at the ASCO Breast Cancer Symposium was a small study
that analyzed the tears of women with breast lumps using a special machine
called a mass spectrometer.38 They
were able to tell who had breast cancer and who did not based on the
results of a protein “fingerprint” of the tears. If
these results are corroborated in further research, women may eventually
be able to say goodbye to their annual mammogram.
Antiviral Therapy for Metstatic Breast Cancer
In recent years, there
is accumulating evidence of a strong link between the human mammary tumor
virus and the occurrence of breast cancer. Researchers
at the National Cancer Institute are testing this hypothesis. They
showed that nelfinavir (Viracept), a protease-inhibiting antiviral drug
commonly prescribed for HIV, caused breast cancer cells to die in laboratory
conditions.39 I hope it will not be long before a human clinical
trial is done to answer this important question more conclusively.
Gwendolyn Stritter, MD, is a clinical advocate for those with difficult
or life-threatening health problems. Her practice is focused especially
on those with breast cancer. She is a member of the American Society
of Breast Disease, the Society for Integrative Oncology, the American
Society of Clinical Oncology, and the American Pain Society. Dr. Stritter
would like to thank Michael McCulloch and Autumn Stanley for their
editorial assistance. She would also like to thank Carl Stritter and
Ann Baldwin for reviewing the manuscript. Visit her online at www.strittermed.org.
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