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Breast cancer is a serious and significant disease and I’ve worked with many brave women to battle against it. If you’re a frequent reader of this blog, you know that I like to cite recent studies and researchers to illustrate some new treatment trends. I first met Sharon as a result of my search for additional therapies as I started my fight against breast cancer.
There is no better reward than knowing my acupuncture and Oriental Medicine services have had an impact on a patient’s life. The Breast Cancer Program at UH Seidman Cancer Center located on the campus of UH Case Medical Center is enhancing and increasing opportunities for clinical research in new therapies and molecular technologies as we move toward a program in personalized medicine for our patients with breast cancer. Personalized medicine begins even before diagnosis, as soon as we recognize the presence of a high-risk predisposition to breast cancer. When screening confirms that someone is at high risk of developing breast cancer, for example, due to the presence of an inherited gene like BRCA1 or BRCA2, we offer additional specific testing to clarify the individual’s actual genetic predisposition. Our Breast Cancer Program merges our broad clinical experience with breast cancer with a state-of-the- art understanding of molecular biology – moving toward whole genome sequencing in patients who are potentially at high risk of developing this disease.
For breast cancer patients, we also focus on the genetics and genomics of their cancers to personalize their treatment. One study opening early in 2013 through the Case Comprehensive Cancer Center will enroll women with stage 2 or 3 breast cancer. We present the cases of all of our breast cancer patients to the entire multidisciplinary tumor board team to reach decisions about optimal therapy. Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. I think the best “expert” in this regard is a brave patient that has lived through this battle. Here’s to our continued, collective success in melding old and new and traditional and alternative to triumph over breast cancer.
These biomarkers are interpreted within the relevant signaling pathway to identify a potential vulnerability for the cancer.
Identifiable genetic abnormalities predict that certain women and men will develop breast cancer. We help our patients become fully informed about their true risk through evaluation, counseling and genetic testing, if it is appropriate. We want not only to identify known genes but also discover potential new genetic predictors.
And when indicated, our imaging group offers clinical trials in nuclear imaging and PET-MRI for the evaluation of response to treatment. They will be offered preoperative therapy in an attempt to shrink the tumor and improve surgical outcome.
Using a genomic fingerprint of an individual’s cancer, not just the determination of the presence or absence of receptors on the tumor cells, is the most up-to-date approach to this type of predictive testing. We plan to offer these women a resequencing or repeat analysis of the recurring tumor to help decide the best targeted therapy to treat the recurrence, also as part of a new clinical trial. For patients enrolled in our genomics clinical trials, we additionally will convene a multidisciplinary genomics tumor board, with representatives from surgical, medical and radiation oncology as well as pathology, cancer genetics and bioethics. Harris has focused her research into the genomic aspects of breast cancer and the development of novel strategies to evaluate and treat breast cancer. I did not take any of my anti-nausea medications or any other pharmaceuticals to help with side effects. The UH Seidman Cancer Center’s genetics program screens and consults with individuals in the community who think they might be at high risk for breast cancer.
Shenk’s clinic follows these patients to make sure they have access both to the most advanced screening for breast cancer and to novel clinical trials designed to develop new means of preventing breast cancer.


Her research includes the validation of a new 6-gene signature, discovered in her laboratory, that predicts complete response to trastuzumab, the molecular classification of response to therapy in HER2-positive, early stage breast cancer, and clinical trials investigating optimal therapy for various types of breast cancers.
More sobering is the fact that the NCI data shows that Philadelphia county has our state’s highest age-adjusted death rate for breast cancer at approximately 29-34 women per 100,000 residents. Using this east-meets-west strategy, I’ve had the privilege of helping several patients successfully battle their disease and help treat some of the most uncomfortable aspects of cancer – pain, nausea, fatigue and depression. We can help those individuals who want to know how quantifiable that risk is and what their options are to help reduce their risk of developing cancer. When a patient wishes to participate in a clinical trial, the navigator will explain details of the trial, genetic and genomic testing, the results of those tests, and the implications of those results for the patient and family members, as well as the details of the personalized treatment that is recommended. The good news is that these rates have actually been improving for Philadelphia, so there’s hope for further progress. I did not experience the fatigue to the extent that most talk about with radiation and the results from treating the surgical scar tissue have been truly amazing and I am so happy. Harris came to UH Seidman Cancer Center from Yale, where she served as Head, Breast Medical Oncology, The Breast Center at Smilow Cancer Hospital at Yale-New Haven, and Co-Leader, Cancer Genetics and Genomics, Yale Cancer Center; and Associate Professor of Medicine, Medical Oncology, Yale Medical School. At UH Seidman Cancer Center, she is the Director of the Breast Cancer Program and holds the endowed Diana Hyland Chair for Breast Cancer, and at Case Western Reserve University School of Medicine, she is Professor of Medicine, Hematology and Oncology. She was treated with a combination of gene targeted and cytotoxic chemotherapy including capecitabine, erlotinib, bevacizumab and phenylbutyrate. She is the principal investigator for several phase I, II and III clinical trials for the treatment of advanced breast cancer.
She tested weakly positive for HER-2 despite prior negative FISH, which prompted us to add trastuzumab to her regimen. Baseline CT revealed five liver tumors—the sum of the products of the two largest perpendicular diameters was 110 cm2. More than 50% decrease in tumor size persisted on two follow-up CT scans, confirming partial response. A group of 16 women, including this patient, diagnosed with triple negative breast cancer with distant metastases were treated by our team with a combination of gene targeted therapy and chemotherapy. Six percent of patients obtained partial response, 25% minor response, 31% stable disease, and 38% progressive disease. The median duration of treatment in patients who relapsed after the second-, thirdand fourthto seventh-lines of chemotherapy was 59 weeks, 22 weeks and 17 weeks, respectively. Comparison of results obtained with cytotoxic chemotherapy revealed that MDT in the secondand third-lines was only nine and four weeks, respectively. In conclusion, this case report indicates that it is possible to obtain durable objective response of recurrent TNBC with a combination of gene targeted agents.1. IntroductionGene expression studies have identified multiple subtypes of breast cancer with different “genetic signatures” [1,2].
Triple-negative breast cancer (TNBC) which does not over-express HER-2 (human epidermal growth factor receptor 2), estrogen receptor, or progesterone receptor creates the biggest challenge in the treatment of metastatic breast disease [3].
Patients diagnosed with TNBC have shown an inferior prognosis with the increased likelihood of distant recurrence including brain metastases within five years of diagnosis. The mean time to distant metastases with TNBC is approximately 50% shorter than that of other breast cancer groups [1]. The mean time to death for patients diagnosed with TNBC is 4.2 years compared to 6 years for other groups [1].
Due to the absence of specific genetic markers, gene-targeted therapy is not often used for TNBC compared to other cancers.
Patients with TNBC relapse quickly on chemotherapy, and, as a result the median duration of treatment (MDT) was proposed as a surrogate for duration of treatment response [4,5]. The feedback up-regulation of compensatory signaling networks has been observed with single gene targeted agents that were not successful in the treatment of TNBC.


Case ReportIn January 2007 a 56-year-old Lebanese female was diagnosed with invasive high-grade TNBC with regional lymph node metastases. Her initial treatment included lumpectomy, TAC chemotherapy (six cycles of docetaxel, doxorubicin, and cyclophosphamide), reexcision, and radiation therapy, through September 2, 2007, which resulted in complete response.
Follow-up CT revealed decreased tumor size and by May 8, 2008 PR was reached (62% decrease of the total tumor load) (Figure 2).
Figure 2 represents a CT of May 8, 2008, which documents a marked decrease of the lesions.More than 50% decrease persisted on CT scans of July 7 and September 26, 2008. Her radiological improvement coincided with disappearance of symptoms, reduction of tumor markers, and normalization of liver tests. Capecitabine and erlotinib were discontinued, and replaced by lapatinib 750 mg po daily, sorafenib 200 mg po bid, and vorinostat 100 mg po daily. DiscussionThis patient failed combination chemotherapy with both anthracyclines and taxanes. The logical choice was the treatment with capecitabine, which is FDA-approved for such condition and recommended for TNBC [10]. The diagram presented on Figure 4 provides a graphic explanation of the rationale for the treatment of this patient. Cancer growth stimulatory signals are represented by red arrows and inhibitory interventions by green arrows and break symbols. Likewise cancer growth stimulatory proteins are shown in red and yellow, growth factor receptors in yellow and oncogene products in orange. Six percent of patients obtained PR, 25% minor response, 31% stable disease (SD), and 38% progressive disease (PD). The MDT in the second-, third-, and fourthto seventh-lines was 59 weeks, 22 weeks, and 17 weeks, respectively.
Comparison of results obtained with cytotoxic chemotherapy reveals that MDT in the secondand third-line was only 9 and 4 weeks, respectively [5]. The treatment was tolerated very well, and in the majority of cases resulted in symptomatic improvement. ConclusionsThis case report indicates that it is possible to obtain an objective response in the treatment of recurrent TNBC with a combination of gene-targeted agents.
The selection of medication based on the determination of expression of the most important oncogenes was successful in accomplishing the disease control rate of 62% (PR + minor response + SD) in a group of 16 women diagnosed with TNBC with distant metastases. The MDT in this group was substantially longer in comparison with MDT reported for cytotoxic chemotherapy. These findings may have implications for the design of clinical trials involving molecular profiling of individual patients withFigure 4. Narod, “Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence,” Clinical Cancer Research, Vol.
Carey, “Triple-Negative Breast Cancer: Risk Factors to Potential Targets,” Clinical Cancer Research, Vol. Bousoulegas, “VEGF-A, VEGF-C, VEGF-R2, EGFR and HER2 in Serum Plus EGFR in Tissue of Patients with Triple-Negative Breast Cancer,” Breast Cancer Research, Vol. Dent, “Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation,” Clinical Cancer Research, Vol. Bhalla, “A Novel Combination Therapy with Histone Deacetylase Inhibitor and Aurora Kinase Inhibitor for ‘Triple Negative’ Breast Cancers,” Cancer Research, Vol.




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