Breast cancer pathology

Keeping up with the advances in molecular pathology – Interview with Dr. Diganta Hazarika

“Androgen receptor (AR) is a steroid nuclear receptor and is expressed more frequently than ER in breast cancer. Although the precise role of AR in breast carcinogenesis is not clear, the possibility of it serving as a therapeutic target, especially in TNBC, is of significant interest and many trial studies are in progress.”

Our guest this week is Dr. Diganta Hazarika, a Senior Consultant Onco-Pathologist at HealthCare Global Enterprises Ltd (HCG), Bangalore.

Dr. Hazarika is a well-known Onco-Pathologist with over 35 years of experience. In addition to his clinical responsibilities, Dr. Hazarika is a registered PhD guide at the Rajiv Gandhi University of Health Sciences in Bangalore with over 20 publications in national and international journals.

Dr. Hazarika – Welcome! It’s great to have you with us. Please tell our readers about yourself and your role at HealthCare Global Enterprises.

I completed my MD Pathology from the Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh in 1983. I have been Professor & Head, Dept. of Pathology at Kidwai Memorial Institute of Oncology, Bangalore since 2010. I am also a Senior Consultant Onco-Pathologist at Health Care Global Enterprises Ltd (HCG) in Bangalore.

HCG is one of India’s premier cancer hospitals present in 20 locations across India. The Pathology department of HCG functions as a Reference Laboratory with a mission to deliver the highest quality lab results to meet the needs of cancer patients in a cost effective and personalized manner. Our lab is NABL and CAP accredited. I work in the surgical pathology wing, where I render primary diagnosis and second opinion services involving histopathology, frozen section, cytology and immunohistochemistry (IHC). I take independent decisions of difficult, rare and unusual cases. My area of interest is Lymphoma, Breast, Bone & Soft tissue sarcoma.  I take active part in all academic activities of the Institute including Tumour Board and MDTs. I am a Course Director of the Diplomate of National Board DNB for Pathology and Onco-Pathology fellowship courses.

Can you please comment on the incidence of breast cancer in India? What diagnostic tools are used for evaluation?

Incidence of Breast cancer in women is 27% of all cancers in India.  Adenocarcinoma (Invasive Ductal Carcinoma) is the most common sub type.

Triple assessment is used for diagnostic procedure, comprised of clinical examination, imaging and a tissue biopsy.

  • Clinical assessment- the initial step is to take history and perform physical examination.
  • Imaging- Palpable masses are imaged before a biopsy is done. The extent of imaging depends on age and risk status and degree of clinical suspicion.  For this purpose, our Radiology department is equipped with Ultrasound (for cyst), Digital Mammography, MRI, and CT/PET CT scan.
  • Tissue Biopsy- the decision to perform a biopsy is based on clinical appreciation of a palpable mass, irrespective of imaging findings. FNAC is discouraged in our Institute, Core-Needle biopsies are preferred for  primary diagnosis, and ER,PR, HER-2 and Ki-67 status are evaluated by default, which aids for NACT and conservative breast surgery with a clean surgical margin(Lumpectomy, SLND/Axillary clearance). Frequently, core needle biopsies are facilitated  by stereotaxis or ultrasound image guidance. Mammotome is used in selected cases.

For HER2-positive breast cancers, what is your experience of the concordance between IHC (Immunohistochemistry) and FISH (Fluorescence in situ hybridization)?

Our lab is committed to generating reliable and reproducible test results for HER-2 determination.  It is performed according to recommendation of CAP guidelines and we undergo CAP proficiency testing for the same. We conducted a pilot study, comprised of 218 cases to evaluate concordance between IHC and FISH. Concordance rates were 97.6 % for IHC 1+  (HER-2 negative), 87% for IHC 3+ (HER-2 positive) and 43% for IHC 2+ (HER-2 borderline). Our results are similar to others, published in world literature. For cases in which the IHC result is indeterminate (scored as 2+), we perform reflex test by FISH for HER-2 gene amplification. We are very much concerned about the effects of fixation on antigenicity, false-positive and false- negative results and subjectivity of scoring. Our goal is to achieve a greater than 95% concordance between IHC negative/FISH – and between IHC 3+/FISH + results.

With triple-negative breast cancers (TNBC), what treatment options are available for androgen receptor positive or negative patient subsets?

Androgen receptor (AR) is a steroid nuclear receptor and is expressed more frequently than ER in breast cancer. Although the precise role of AR in breast carcinogenesis is not clear, the possibility of it serving as a therapeutic target, especially in TNBC, is of significant interest and many trial studies are in progress. Clinically, AR positivity is associated with better prognosis and associated with a lower recurrence score using the 21-Gene test. Though AR assessment in our hospital is not a part of routine pathological testing for breast cancer, we have done  a pilot study, utilizing AR IHC (immunohistochemistry) expression, encompassing 114 cases, and approximately 23% of TNBC, were classified as AR molecular subtype. AR targeting drugs – Bicalutamide/ Enzalutamide are available in the market, and in clinical trials have demonstrated early promise in selected TNBC cases. They are mostly used in prostate cancer, not in TNBC cases in our hospital.

What prognostic or predictive genomic biomarkers are being used for optimizing treatment for individual patients?

The Pathology department. has equipment for higher end molecular biomarker tests for genomics like Sanger sequencing PCR, NGS (Illumina) and Droplet PCR.  A multigene genomic test, comprised of 48 genes has been developed in house, and validated for clinical practice, especially for personalized targeted therapy. Droplet PCR is being used for circulating tumour DNA for evaluation of minimal residual disease (MRD) and TKI resistant lung adenocarcinoma. Routinely EGFR, K-ras, N-ras, BRAF are done for colorectal carcinoma and PDL-1, ALK, EGFR, Rose1 are performed for Non-small cell lung cancer. Organ specific  genomic panels for ALL/AML , DLBCL, MDS, Tumour mutational burden (TMB) are in pipeline for development and validation for clinical applications. Using the Illumina Next Generation Gene Sequencing (NGS) platform, we have developed a multigene genomic panel of 48 genes. For breast carcinomas, ER, HER-2, and PI3K are incorporated in this test. However, for germ line mutations, separate tests for BRCA1 and BRCA2 are available. OncotypeDx and MammaPrint used for prediction of risk of recurrence in early stage breast cancer is under development and will be validated soon for clinical practice.

How is the uptake of digital pathology? Has the technology been implemented in your lab? Where do you it see it being used?

The technological progress of digital transformation of tissue-based diagnosis has opened a new door for pathologists, from image analysis to automated diagnosis. We are very much excited, it is very much challenging, and it will give us time needed to concentrating on difficult cases for the benefit of needy cancer patients. The implementation of connected AI supported system is still in its childhood. We are in the process of installing a Philips IntelliSite Digital Pathology Scanner in our laboratory. We are planning to perform ER, PR, HER-2 and Ki-67 analysis for breast cancer using additional computational diagnostic software/algorithms for automated immunohistochemical measurement.  We have plans to use the scanner for PDL-1 IHC scoring for NSCLC (non-small cell lung cancer) and assess Tumour-infiltrating lymphocytes by PD-1, CD8 and FoxP3 IHC antibody for colorectal and head & neck carcinomas.

Do you currently deposit your slide data and images towards a database or an archive to support studies on the Indian population?

We store all the paraffin blocks and H/E (and IHC slides if required) of  pathology cases for our archival purposes for more than 5 yrs.  Hard copy reports are kept in the files, also respective soft copy reports can be retrieved from the computers used for Laboratory Information System (LIS).

As we have acquired recently Philips Digital Scanner, now we are planning to use digital platform for keeping microscopic digital images and data in the IT server, which will help improve the workflow of the pathology department, especially for archival data with  images

Lastly, are you open to collaborations and partnerships? Are there specific partnership opportunities that are of interest?

We are open for collaboration and partnership, however it has to be cleared from our Institutional Review Board (IRB)/ Ethical Committee.  Our Bio repository Division, presently has 2,40,000 paraffin blocks , and respective clinical information with follow up data to evaluate clinical outcome. This is mainly comprised of  Breast, Head & Neck and Cervical Cancers. We would be very happy to take new collaborative and partnership opportunities from your end in these said verticals as we have all the required data at hand.

Thanks very much, Dr. Hazarika. It has been great speaking with you.

Disclaimer: Interviews are published unedited or with minimal changes.

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