Epidemiological and survival analysis of triple-negative breast cancer cases in a retrospective multicenter study

http://www.indianjcancer.com/article.asp?issn=0019-509X;year=2016;volume=53;issue=3;spage=353;epage=359;aulast=Sarin;type=0

This is a retrospective study with data collected from breast cancer cases from five major Apollo Hospitals across India, as part of a biobanking process. One aspect of our study focused specifically on data from triple-negative breast cancer (TNBC) cases. The aim of this study was to analyze epidemiology, treatment options, and survival of the patients with TNBC. Our goal was to draw conclusions on the preponderance of the disease and also to understand the outcomes using the existing therapy options. MATERIALS AND METHODS: Data were collected after due ethical clearances and were coded with regard to patient identifiers to protect patient privacy. Data were not only from the various departments of the respective hospitals and the treating physicians but also from the follow-up made by hospital staff and social workers. RESULTS: About 20% of all cases of breast cancer comprised TNBC. Although the disease is generally thought to be an early onset disease, there was no major difference in the median age of diagnosis of TNBC compared to other breast cancer cases. More than 85% of the TNBC cases were of early stage disease with <4% of the cases of metastatic cancer. Data on follow-up were somewhat sporadic as a good number of cases were lost to follow-up, but from the available data, recurrence rate was about 11%. Death, when it occurred, was mostly in the early periods of treatment with 35% of the events occurring before 3 years. The overall survival rates beyond 3 years were more than 86%. CONCLUSIONS: Data and sample collection are an ongoing process, so we expect this data set to be enriched with more cases and longer duration of follow-up in a year. Preliminary analysis sheds light on the potential of such a collection both for understanding the epidemiology of the disease and also for conducting future studies with an eye toward improving treatment outcomes.

Sapien collaborates with Dr. Anjana Rao of La Jolla Institute

It is a pleasure to be working again with Dr. Anjana Rao, Jugnu’s postdoc advisor from Dana Farber Cancer Institute & Harvard Medical School days. Anjana is now the Chair of La Jolla Institute of Allergy and Immunology with a joint appointment at UCSD.  Her lab’s work on Tet family of proteins and their regulation of transcription via methylation in cancer is well known (Rao et al Nat Immunol 2017).

Given our biobank’s deep collection of annotated cancer samples, both FFPE and matched live cells,  it’s a synergistic alliance wherein Sapien brings not just samples but also its R&D expertise in histopathology, cellular and molecular biology to bear on the project.  The project’s first milestone to standardize and automate LJI’s IHC protocol in Sapien hands has been reached.

Sapien Biosciences and OncoStem Diagnostics collaborate to launch CanAssist-Breast, a Breast cancer recurrence prediction test

Hyderabad, November 10, 2016: Sapien Biosciences, a niche biotech venture committed to develop novel cutting-edge medical diagnostics backed by Apollo Hospitals Enterprise Limited announces its partnership with OncoStem Diagnostics, to launch “CanAssist-Breast”, a robust and cost-effective test to predict the risk of breast cancer recurrence in early stage hormone positive and Her2 negative Breast Cancer patients.

Sapien Biosciences is a bio-repository that enables the development of cutting edge diagnostics and therapeutics for personalizing medicine. Patient samples and associated medical data that are systematically collated and ethically banked at Sapien are a necessary resource for rapid validation of novel diagnostic tests. Announcing the partnership with OncoStem Diagnostics Dr. Jugnu Jain, Co-Founder and CEO – Sapien Biosciences said, “We are very excited to be part of this launch of CanAssist–Breast which represents a paradigm shift in customizing Breast cancer treatment. Development of accurate recurrence diagnostics in cancer is particularly dependent on the availability of reliable retrospective information which is acutely lacking in India. To validate CanAssist-Breast, we mobilized five Apollo hospitals data archives to piece together complete 5 years treatment and outcome data for over 6500 Indian breast cancer patients”.

In India, about 1,50,000 patients are diagnosed of breast cancer every year and currently there are no affordable tests to predict the risk of cancer recurring. As a result, majority of early stage patients with low risk of recurrence are perhaps over-treated and thus bear toxic effects of chemotherapy treatment (CT) that reduces their ‘quality of life’. Additionally, studies have proven that the benefit of chemotherapy in such patients is known to be 10-15% suggesting many patients can be spared conventional CT. Highlighting the importance of CanAssist-Breast, Dr. Manjiri Bakre, Founder and CEO, OncoStem Diagnostics said, “CanAssist-Breast is our flagship product and is a boon for patients as well as doctors. It enables clinicians to assess the aggressiveness of the tumor and personalize and optimize therapy for their patients. The canAssist-Breast test can spare over 60,000 Breast Cancer patients in India and over 660,000 patients worldwide every year from the severe effects and unnecessary costs of chemotherapy-associated toxic”.

CanAssist-Breast test uses clinical parameters in combination with novel biomarkers quantified using a standardized technique which measures protein expression accurately. This information is integrated into a statistical algorithm to stratify patients as “low or high risk” for recurrence. “In India, due to a variety of reasons ranging from awareness to culture, Breast Cancer patients are diagnosed much later, with only 5-8% of patients being Stage 1 at detection.  Consequently, the globally available recurrence prediction tests are not very impactful in geographies such as India and SE Asia due to their utility being limited to only Stage 1 patients and the prohibitive cost of the tests. CanAssist-Breast test can be used on a much wider pool of patients up to Stage 2B, and is priced at 1/6th the price of competitor tests and therefore aims to touch the lives of millions of patients worldwide”, added Dr Bakre.

CanAssist-Breast is being launched within the Apollo network in India and the worldwide launch is planned in a phased manner.  Commenting on the partnership, Ms. Shobana Kamineni, Executive Vice Chairperson, Apollo Hospitals says, “Affordable and broad based tests to estimate the ‘risk of recurrence’ are an absolute necessity for ‘optimal and personalized’ treatment planning. Apollo has been at the forefront of recognizing personalized medicine as the future of healthcare delivery and has been adopting cutting-edge diagnostic tests to deliver better patient care to improve outcomes. Our association with Sapien is one of various initiatives we have undertaken with a vision to enable personalized medicine approach and we are very excited to see this crystallize through partnerships such as this one with OncoStem. Cancer recurrence space is largely unexplored, especially in India and needs immediate attention. I look forward to Apollo & Sapien pioneering the introduction & adoption of this important innovation from OncoStem across our network of oncology centres for the benefit of our patients.”

CanAssist-Breast is ISO-13485 accredited, and expects to acquire the CE mark by November 2016.  These accreditations will enable the launch of the test in global markets later this year. The market for a breast cancer recurrence diagnostic space  is currently valued at $ 3 Billion globally and is expected to grow at 18% CAGR.  Clinical validation of CanAssist-Breast in India and the US demonstrates a high NPV (negative predictive value) of 95%, which is a measure of the accuracy of the test. The results of the global validation study are currently under review for publication.

About Apollo Hospitals Enterprise Ltd. (AHEL)

It was in 1983, that Dr. Prathap Reddy made a pioneering endeavor by launching India’s first corporate hospital – Apollo Hospital in Chennai. Now, as Asia largest and most trusted healthcare group, its presence includes over 8,600 beds across 50 Hospitals, 1,632 Pharmacies, 92 Primary Care and Diagnostic Clinics, 100 Telemedicine units across 10 countries. Health Insurance services, Global Projects Consultancy, 15 colleges of Nursing and Hospital Management, a Research Foundation with a focus on global Clinical Trials, epidemiological studies, genetic research and the upcoming first Proton Therapy Center across Asia, Africa and Australia.

In a rare honor, the Government of India issued a commemorative stamp in recognition of Apollo’s contribution, the first for a healthcare organization. Apollo Hospitals Chairman, Dr. Prathap C Reddy, was conferred with the prestigious Padma Vibhushan in 2010. For more than 30 years, the Apollo Hospitals Group has continuously excelled and maintained leadership in medical innovation, world-class clinical services and cutting-edge technology. Our hospitals are consistently ranked amongst the best hospitals globally for advanced medical services and research.

About Sapien Biosciences Pvt. Ltd.

Sapien Biosciences is a joint venture between Apollo Hospitals & Saarum Innovations that has created a world-class biobank and personalized medicine company that leverages Apollo’s leadership position in healthcare and Saarum’s cutting-edge life sciences research expertise for novel clinical and R&D applications. Sapien’s primary objective is to use its high-quality bio-repository that integrates ethically consented human samples with associated medical, pathological & treatment data and utilize this resource to develop & deliver high-end diagnostic applications. Further Sapien has entered into an alliance with Apollo Hospitals that allows Sapien to front-end Apollo’s personalized medicine initiatives. This allows Sapien to bring novel cutting-edge diagnostics to Apollo, either on its own or in collaboration with best-of-breed global institutions world-wide thereby enabling world-class healthcare to improve patient outcomes. Sapien has fully functional labs located within the Apollo Health City Campus in Hyderabad. For more information about Sapien Biosciences, visit www.sapienbio.com.

About OncoStem Diagnostics Pvt. Ltd. 

OncoStem is a start-up diagnostic oncology company.  It is founded by a Dr. Manjiri Bakre, a Cell Biology veteran with significant experience in US, Singapore and India in cancer biology and cancer drug discovery.  It is funded by Artiman Ventures, an early-stage Silicon Valley-based venture fund that invests in white space companies that create or disrupt multi-billion dollar markets. OncoStem is primarily focused on developing novel tests which will predict ‘risk of cancer recurrence’ and thus enable physicians to prescribe targeted drugs to prevent cancer recurrence.  OncoStem’s initial focus is breast cancer as it is the most common cancer in women across the globe but it also plans to develop similar tests for other cancers such as oral, glioma, lung and colon. For more information about OncoStem Diagnostics, visit www.oncostemdiagnostics.com

 

For more information, please contact    info@sapienbio.com , 040-65580008,  9704600772

Human medical waste to build biobanks

http://www.journal.ijmio.com/index.php/ijmio/article/view/132

Jugnu Jain, Sreevatsa Natarajan, Soma Chatterjee

India has a high disease burden and a large number of patients. There is a tremendous need for Indian biobanks to preserve Indian samples, to capture the great diversity of diseases to spur research into earlier, more precise diagnosis and better treatments for diseases plaguing India. This review article summarizes the key components of building a systematic comprehensive biobank, type and formats of sample and data, and the ethical and regulatory guidelines in India. An example of a growing Indian biobank, Sapien Biosciences, is shared along with its business model to reach sustainability. This is done by developing clinical diagnostics internally using the annotated samples but also sharing samples and outcomes data with external investigators. Our goal is to highlight the immense untapped value of Indian biospecimens and data, to catalyze the formation of collaborative networks of biobanks both within and outside India

Sapien collaborates with Boston University to perform cost-benefit analysis of treatment paradigm in PCI Stent patients in the Indian healthcare system

Sapien  is collaborating with Dr. Joglekar’s group  at Boston University  to mine Sapien’s cardiac patients database. Our goal is to jointly analyse patterns of usage of different stents, blood thinning medicines, co-medications, myPlatelet assay , follow-up visits and monitoring with an eye towards optimizing implementation of personalized treatment to improve patient outcomes.

Over the last three years, Sapien Biosciences, working with leading cardiologists Dr. PC Rath and Dr. PK Sahoo at Apollo Hospitals, and Dr. A Yerramilli at SV College of Pharmacy, have collated a detailed dataset of approximately 800 coronary artery disease patients who underwent a PCI-stent procedure. These patients were prescribed various anti-platelet therapies (APTs), branded or generic versions of clopidogrel, prasugrel, ticagrelor, as part of their maintenance regimen for a year or more to prevent restenosis.  About half of these patients also took Sapien’s myPlatelet test (myPlatelet brochure), a combination genetic and functional test, to check the effectiveness of the APTs they were prescribed. These ~800 patients have been followed up for a year to determine the success of their treatment regimens and document any significant adverse events. This rich dataset is being used to perform cost-benefit analysis of different treatment paradigms in the Indian healthcare delivery context.

Appropriate ethical IEC/IRB clearances have been taken by each party to share de-identified data. These analyses are expected to be published and pave the way for additional studies including assessing the impact of patient engagement in improving outcomes.

myPlatelet test is a combination of genetic profiling for the presence of common variants of CYP2C19 gene that affect the bioavailability of clopidogrel , and a platelet function test for evaluating platelet reactivity.  It is highly specific and sensitive compared to the commonly used Light Transmission Aggregometry (LTA), and correlates well with the plasma levels of anti-platelet medication. It is able to detect high risk of thrombosis or blood clotting as well as excessive bleeding. The value of this assay in preventing post-procedural major adverse cardiac events or MACE in patients who underwent PCI has been demonstrated in several studies world-wide as summarized in this publication.

Sapien is India’s largest commercial biobank, repurposing human medical waste to discover and validate clinically useful prognostics, diagnostics & theranostics to optimize the diagnosis and treatment of individual patients. It has curated over 55000 patients’ samples and associated data spanning most diseases plus access to more than 1.5 million healthy and diseased individuals. It follows Indian medical council (ICMR) guidelines and works closely with Institutional Ethics Committees to ensure ethical and regulatory compliance.

Dr. Nitin Joglekar  is Associate Professor of Operations and Technology Management, and Dean’s Research Fellow, at Boston University Questrom School of Business. His interests span development of products, supply chains and customer engagement at established and entrepreneurial organizations.

Industry Internships for Motivated Biology-Based Graduate Students

Jugnu Jain
CEO at Sapien Biosciences & Saarum Sciences

We offer 2 to 12 month research internships for bright diligent motivated graduate students in Biology, Biotech, Pharmacy, Bioinformatics, Health data analytics etc. The internships can be hands-on lab experience (molecular biology, cell biology, diagnostics, FACS etc.), or in medical data analysis, sample and clinical data organization in EMR/EHR databases. Specific clinically-relevant projects focused on patient treatment paradigms e.g., breast cancer, stent procedures drugs and outcomes, cost-benefit analysis of targeted drugs are also available.

Lab-based training is available at Hyderabad, whilst data and project-based training is available at Ahmedabad, Bangalore, Bhubaneswar, Chennai, Delhi, Kolkata and other metro locations where Apollo Hospitals are present.

Appropriate ethical approval for projects involving handling of patient material or data is always taken. Students are trained in confidentiality and safety norms.

In addition to a certificate of internship and thesis, students are encouraged to present their findings in conferences. Longer-term interns that make significant contribution to projects may also be acknowledged in presentations and publications from our group. Mentoring of students aspiring for MS/PhD abroad is done on a case-by-case basis.

Our first paper on breast cancer is accepted for publication

Jugnu Jain
CEO at Sapien Biosciences & Saarum Sciences

“Epidemiological and survival analysis of triple negative breast cancer cases in a retrospective multicentre study” comprising 257 TNBC cases collated from across five cancer centres in India has been accepted for publication. It should be out in a few months.

Next one summarizing data from >6500 Indian breast cancer cases, of all receptor types, is under preparation. Our goal is to exceed 10,000 cases within the year.

Our database of breast cancer samples, complete diagnosis and treatment info, combined with 3-5 year outcomes data offers tremendous opportunity to study Indian risk factors, identify optimal treatment paradigms for each subtype of patients, analyze cost-benefit ratio of different surgical/chemo/RT treatments, etc. We expect using them to also develop better prognostic, diagnostic and theranostic tests to improve survival in breast cancer patients.

Stay tuned!

Breast cancer in low-income countries: India as a model

Abstract:

Background: Developing countries contribute substantially to breast cancer mortality worldwide, as early-stage diagnosis and effective adjuvant therapies have decreased breast cancer-specific mortality in developed countries. Unfortunately, the costs of breast cancer screening programs and treatments limit translation of these results to developing nations. Methods: We retrospectively analyzed the tumor characteristics and modalities of management in 454 patients with Stage I-III invasive breast cancer in a single tertiary cancer center (Rajiv Gandhi Cancer Institute & Research Center) in New Delhi, India treated in 2010.

Results: The median age at diagnosis was 52 (range 25-88). Stage II tumors predominated, with tumors ≤ 5 cm in size in 93% of patients. 84% of patients underwent modified radical mastectomy, while 14% underwent breast-conservation therapy (BCT). Overall, 79% of patients received adjuvant or neo-adjuvant chemotherapy and 49% received radiotherapy. Receptor characterization revealed: ER+/PR+/Her2-, 52.9%; ER+/PR+/Her2+, 10.2%; ER-/PR-/Her2+, 13.8%; and triple-negative, 23%. Of the ER+/PR+ patients, 58% were node-positive, 79% received chemotherapy and 100% were advised hormonal therapy. Of the Her-2 positive patients, 23% received trastuzumab.

Conclusions: Breast cancer management strategies vary in Indian and US populations. Indian patients are younger with tumor sizes amenable to BCT followed by loco-regional radiotherapy. Despite this, only a minority of patients opted for BCT. In the hormone-positive population, majority of patients received chemotherapy in addition to hormone therapy due to high incidence of node positivity, tumor size>2 cm and unaffordability of genomic assays. In the Her2+ population, trastuzumab use was limited, reportedly due to cost. Overall, management is adapted to limited resources and follow-up is inconsistent. It may be beneficial to set up Indian national breast cancer guidelines to promote multidisciplinary management, describe the molecular features of disease in this population, and evaluate the cost-effectiveness of expensive diagnostic and therapeutic interventions. This will encourage rational policies and help to create a comprehensive cancer treatment network.

Source: http://meetinglibrary.asco.org/content/132656-144

Citation:
J Clin Oncol 32, 2014 (suppl; abstr e17517)

Author(s):
Mahasweta Gooptu, Dinesh Doval, Kapil Kumar, Ajay Dewan, Anurag Mehta, Ullas Batra, Kumardeep Dutta, Tiffany P. Avery, Rebecca J. Jaslow, Edith P. Mitchell, Afzal Naiyer, John Manavalan, Massimo Cristofanilli; Thomas Jefferson University, Philadelphia, PA; Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India; Department of Medical Oncology, Rajiv gandhi cancer Institute and Research center, Delhi, India; Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA; Star Health Network, New York, NY; Kimmel Cancer Center at Jefferson, Philadelphia, PA

A Targeted Agent for Triple-Negative Breast Cancer

Glycoprotein NMB (gpNMB) is a transmembrane protein and tumor-associated antigen that is expressed at higher levels in certain malignancies than in normal tissues. Glembatumumab vedotin (CDX-011) is an antibody-drug conjugate consisting of a fully human IgG2 monoclonal antibody against gpNMB linked to the microtubule inhibitor monomethyl auristatin E (MMAE). By targeting and binding to cells overexpressing gpNMB, the antibody is internalized, allowing for intracellular release of the cytotoxic MMAE.

A prior phase I/II trial of CDX-011 for refractory advanced breast cancer demonstrated an acceptable toxicity profile and an objective response rate (ORR) of 12% (NEJM JW Oncol Hematol Nov 2014 and J Clin Oncol 2014; 32:3619). In the subset of patients with triple-negative breast cancer (TNBC), the ORR was 20%, and progression-free survival (PFS) was 4.1 months; in TNBC patients with gpNMB-expressing tumors the ORR was 25%, and the PFS was 5.1 months. Now, investigators have conducted an industry-supported, randomized phase II trial (EMERGE) of CDX-011 versus investigator choice of chemotherapy (IC) in 124 refractory breast cancer patients with tumors overexpressing gpNMB (defined as ≥5% of malignant epithelial or stromal cells with any expression).

ORR was similar overall for patients receiving CDX-011 or IC (6% and 7%, respectively) and for those with gpNMB-expressing tumors (12% for both). ORR was higher with CDX-011 versus IC in patients with ≥25% of tumor cells expressing gpNMB (30% vs. 9%) as well as in TNBC patients (18% vs. 0%) and TNBC patients with overexpression of gpNMB (40% vs. 0%). Dose reduction occurred in 25% of patients in both treatment arms. The most common CDX-011 toxicities were rash, fatigue, nausea, neutropenia, and neuropathy.

Comment
The attraction of targeted therapy with an antibody delivery system is that it directs the cytotoxic agent preferentially to the malignant cell population, potentially enhancing efficacy and minimizing systemic toxicity. The use of ado-trastuzumab emtansine for HER2-positive breast cancer demonstrates the success of this approach (NEJM JW Oncol Hematol Sep 2014 and J Clin Oncol 2014; 32:2750). The signal that CDX-011 is active in TNBC is exciting, but the observations from this study are based on very small numbers of patients. A larger, pivotal phase II trial (METRIC) is under way to more fully investigate this compound in TNBC.

Citation:
Yardley D et al. EMERGE: A randomized phase II study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB–expressing breast cancer. J Clin Oncol 2015 Apr 6; [e-pub]. (http://dx.doi.org/10.1200/JCO.2014.56.2959)

ROS1 rearrangements occur in approximately 1% of patients with NSCLC

The Promising Therapeutic Strategy against ALKoma and ROS1-positive Tumors

It has recently been identified that crizotinib significantly inhibits the tumor cells with ALK-fusion genes or ROS1-rearranged driver genes which encode constitutive tyrosine kinase receptors. The emerging concept of lung cancer stem cells (CSCs) arises a question of the relationship between CSCs and ROS1 gene rearrangement.

Lung non-small cell cancers are likely to develop due to the fusion genes characterized by EML4-ALK, which suggests the importance of fusion genes in tumorigenesis in the same way as chronic myeloid leukemia (CML) with Philadelphia chromosome derived from t(9;22).

On the other hand, EGFR signal pathway is hyper-activated in lung cancer cells or head and neck squamous cancers. EGFR and CD44 variant (CD44v) expression shows the inverse pattern, and furthermore, CD44v-positive CSCs are refractory to reactive oxygen species (ROS)-induced cellular senescence and apoptosis. It remains to be known the way crizonitib relatively inhibits which sub-population of tumor cells.”

Content Source: Originally posted in “Cancer Targets & Therapeutics Society” LinkedIn group by Jean Plante

Citation: http://www.nejm.org/doi/full/10.1056/NEJMoa1406766