The Avon Foundation for Women has
awarded Einstein and Montefiore pathology researchers Rachel Hazan, PhD, and
Susan Fineberg, MD, a $300,000 grant to facilitate their collaborative research
study of triple negative breast cancer, in primary tumors as well as in the
On Sunday, October 17, Dr. Fineberg
accepted an oversized check before a cheering crowd of thousands adorned in pink that gathered at
Pier 84, in Manhattan, for the closing ceremony of this year’s AVON 39 The Walk
to End Breast Cancer.
This year, over 3,500 enthusiastic men,
women and children walked the 39 mile course over two days, raising $8.7
million to help fund breast cancer research.
Many walked in honor of loved ones they have lost to stage IV breast
“When I said the word metastasis – boom! – thousands of people
were screaming and yelling,” said Dr. Fineberg, an associate clinical professor
of pathology and attending surgical pathologist specializing in diagnosing
breast disease at Montefiore Medical Center.
“When people saw me walking away with that giant check they said they
were so happy to see that the money that they raised is going toward improving
the quality of treatment for stage IV breast cancer,” she added. “I felt humbled
and inspired by the experience, to see how our work had the potential to
improve the lives of so many women.”
A collaborative effort
Dr. Rachel Hazan
professor of Pathology and principal investigator, said the grant
will go toward studying the role of cell cycle inhibitor P21 in triple negative breast
cancer, with a focus on metastatic disease.
“Using models of breast cancer metastasis and metastatic
cancer specimens from stage IV disease, we are finding out that a highly
unsuspected molecule which normally inhibits tumor cell proliferation is
actually playing an aggressive role in metastasis,” said Dr. Hazan, who was in China as an invited guest speaker at the Hangzhou International Conference on Precision Medicine of Cancer Diagnostic and Treatment, in Shanghai, and could not attend the Avon event. Her Einstein lab has made major strides in the last few
years in understanding the underlying causes of cancer metastasis.
breast cancer is considered incurable and triple negative cancers have the
highest incidence of metastasis because they are often resistant to
chemotherapy. Currently, there are no effective
targeted treatment options. Triple negative breast cancers account for 22 percent
of the cases among black women, and 11 percent among white women. The rates of the disease are higher than the
national average in the Bronx, where there is a large population of African
Dr. Hazan’s multidisciplinary
research program focuses on molecular pathways governing metastatic
dissemination of breast cancer. Using
N-cadherin as a model for metastatic progression, her laboratory uncovered key
pathways governing motility, invasion, epithelial to mesenchymal transition,
tumor cell survival and cancer-stem cell evolution, all converging into a
complex network of pathways leading to metastasis. In the process of
investigating N-cadherin function in cancer, her lab’s research led to the
discovery of novel pathways that counteract metastasis independently of
N-cadherin. One such example is R-cadherin, Akt isoforms, and the cell cycle
inhibitor p21CIP1, discoveries that are opening novel and exciting avenues of
Her studies have shown that cell lines in which the P21
was removed lost the ability to metastasize. When the p21 was restored,
however, the cells again exhibit the ability to metastasize. Currently drugs under development target the molecular
pathways under the control of stem cell promoting gene P21, including genes
belonging to the Wnt signaling pathway.
“By targeting these P21 associated
pathways the hope is that this can disrupt the ability of the stem
cell for continued self- renewal and hence inhibit metastasis,” Dr. Hazan said. Alternatively,
targeting the p21/Frizzled axis could be a treatment strategy against triple
negative breast cancer (TNBC).
In order to confirm that P21
expression conveys stem cell properties in vivo, the lab will investigate expression of
P21 high grade triple negative breast cancers to
determine if P21 expression correlates with development of
metastatic disease as well as chemo resistance.
Dr. Fineberg will select the most appropriate tumor tissue
specimens for P21 assessment as well as interpret levels of p21 expression in
these tissues via immmunohistochemistry.
Her expertise in interpreting pathology of breast cancer will allow the
team to correlate appropriate pathologic features of tumors with expression
levels. Also lending his expertise is world renowned breast oncologist Dr.
Joseph Sparano, who is vice chairman of medical oncology at Montefiore
Einstein Center for Cancer Care, professor of medicine and of obstetrics
and gynecology & women's health at Albert Einstein College of Medicine and
associate director of clinical research at the NCI-designated Albert
Einstein Cancer Center.
Dr. Joseph Sparano
This scientific team is among Montefiore’s finest. Drs. Hazan,
Sparano, and Fineberg have spent their entire careers focused on breast cancer
research and hope their work will eventually help in the development of
targeted treatment strategies for triple negative breast cancer.
“Once we can
establish this clinical relationship we can look at the effect of experimental
drugs targeting these pathways to determine if this results in diminished
metastability,” said Dr. Hazan. “We are hoping that this might be extended to
clinical trials for patients with carcinomas at high risk for metastasis and
showing high P21 expression.”
Meanwhile, the Montefiore-Einstein collaboration has fostered new
friendship. For the last few years, Drs. Hazan and Fineberg have met after
hours at Montefiore to look over slides and new cases of triple-negative
patients. They say the basic science and clinical collaboration is highly productive
– but also invigorating and fun.
Dr. Fineberg said, “Rachel says, ‘It’s more fun than going out to
have a glass a wine. We love our work! ”
BOLD BUDDY Patient Navigation Grant
The Avon Foundation for Women has also awarded Alyson Moadel-Robblee, PhD, associate professor of Clinical Epidemiology, a $100,000 Patient Navigation grant for her BOLD Buddy Peer Navigation Program, which trains cancer survivor volunteers to provide peer support to newly diagnosed cancer patients. The Avon grant will help augment the program to address the unique needs of advanced stage and end-of-life breast cancer patients.