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

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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

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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

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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

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Apollo Hospitals & Saarum Innovations launch Sapien Biosciences

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Welcome to Sapienbio Blog

This article originally appeared in 2013

Joint Venture to create a world-class human bio-bank and personalized medicine company, first of its kind in India to enableinnovative research & clinical applications

Hyderabad, September 23, 2013:

Apollo Hospitals with Saarum Innovations, launched its joint venture ‘Sapien Biosciences’ today at Hyderabad to create aworld-class bio-bank and personalized medicine company. The bio-bank will comprise of collections of high-quality, ethically-consented and anonymized human samplesalong with associated medical & sample-level data across various diseases e.g., cancer, cardiovascular and diabetes. This will enable cutting-edge life sciences research and support the discovery & development of novel biomarkers, diagnostics & personalized medicine applications.Sapien plans tocollaborate with healthcare enterprises and drug discovery companies globally to study disease epidemiology, validate new diagnostics, identify new drug targets and evaluate new drugs.

Sapien has exclusive access to the entire Apollo network for its bio-banking needs but expects to partner with additional research-oriented hospitals and clinics for their personalized medicine and bio-banking needs. 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 institutions world-wide thereby enabling world-class healthcare and improving patient outcomes.

Speaking on the occasion, Ms. Shobana Kamineni, Executive Director, New Initiatives, Apollo Hospitals, said, “This is a proud moment for us at Apollo to be a part of this landmark initiative in the history of Indian Health care. Apollo Hospitals has long had a vision of creating Asia’s largest bio-bank which is being realized in partnership with Saarum Innovations. Sapien will help fulfill our vision of delivering better clinical outcomes through bench-to-bedside innovation. This alliance is a further validation of Apollo’s commitment to research-driven health care.”

Speaking on the occasion Mr. Sreevatsa Natarajan, Co-founder & CEO, Sapien Biosciences said “Saarum Innovations is proud to be associated with a healthcare pioneer & leader like Apollo Hospitals. Apollo’s passion for world-class healthcare combined with Saarum Innovations’ proven research expertise will bridge healthcare & life-sciences and enable cutting-edge research & diagnostics applications.”

Speaking on the occasion, Mr. Seemant Jauhari, CEO of AHERF said, “Apollo, through the Apollo Health Education & Research Foundation (AHERF), is spearheading a vibrant portfolio of innovative projects that will enable effective and affordable technologies for better treatment outcomes. Bio-banking & personalized medicine was one such initiative which is being realized with the launch of Sapien Biosciences.

Sapien Biosciences also announces the launch of its first & novel personalized medicine test,‘myPLATELET, which determines patients’ response to their blood-thinning medicationand supports decision-making by their cardiologists to personalize therapy for better outcomes. This is the only test in India that combines both genetic and platelet function response to enable tailored anti-platelet therapy for each patient.

Speaking on the occasion Dr. Jugnu Jain, Co-founder and CSO, Sapien Biosciences said “Sapien’s novel myPLATELET test offers more complete assessment of a patient’s platelet response than existing tests and enables informed clinical decision-making thus exemplifying Sapien’s approach to personalized medicine innovation.”

About Saarum Innovations

Saarum Innovations has been set-up with the vision of utilizing human tissues, primary cells and stem cells to better understand disease biology, develop novel biomarkers and diagnostics, discover novel drug targets and drugs therapeutics that translate into better clinical successes. It is co-founded by a team of three seasoned life sciences R&D professionals,Sreevatsa Natarajan, Prithi Rajan and Jugnu Jain who collectively have over 60 years of global R&D experience.

Sapien Biosciences is managed by the Saarum Innovations team with Sreevatsa Natarajan as the Co-founder & CEO, Jugnu Jain as the Co-Founder & CSO, and Prithi Rajan as the Co-Founder & Executive Director.For more information about Sapien Biosciences, please refer www.sapienbio.com

About Apollo Hospitals

In 1983, Dr Prathap C Reddy, the architect of Indian healthcare, launched the first corporate hospital in India. An integrated healthcare company, the Apollo Hospitals Group has over 8,500 beds across 50 hospitals, more than 1200 pharmacies and 100 diagnostic clinics, medical business process outsourcing services, health insurance services, and clinical research divisions with a focus on epidemiological studies, stem cell research and genetic research. To develop talent for the burgeoning need of superior healthcare delivery, the Apollo Hospitals Group has 11 nursing and hospital management colleges. These accomplishments have earned Apollo Hospitals Group accolades such as the Centre of Excellence from the Government of India and recognition from the Joint Commission International (seven of our hospitals are JCI accredited). In a rare honor, the Government of India issued a commemorative stamp in recognition of Apollo’s contribution, the first for a health care organization. Apollo, for over 27 years, has continuously excelled and maintained leadership in medical innovation, world-class clinical services and cutting edge research. Our hospitals are consistently ranked amongst the best hospitals globally for advanced medical services. For more information visit www.apollohospitals.com