Histological Distribution of Sapien’s Ovarian Cancer Cases

Ovarian cancer is comprised of various tumour groups that are histologically distinct which is important to know for their treatment. The cancer may originate in one or both ovaries, as well as in the nearby fallopian tubes or peritoneum. Diverse types of ovarian cancers are categorized based on the originating cell’s name.

Epithelial ovarian carcinomas, known as cancerous epithelial tumours, are the most prevalent among ovarian cancers. The American Cancer Society states that approximately 85 to 90 percent of ovarian cancers originate from epithelial cells that encase the outer surface of the ovary. Sapien ovarian cancer data of 1445 cases also shows that 95% of cases constitute epithelial tumours while only 5% are non-epithelial tumours such as germ cell and stromal tumours. Among epithelial tumours, 55% are identified as serous, followed by endometroid, adeno, mucinous, and clear cell carcinomas. In contrast, 64% of non-epithelial tumours are germ cell tumors and 36% are stromal tumors.

BRCA1/2 testing can guide therapy in Ovarian Cancer

Homologous recombination repair (#HRR) pathway repairs double-strand DNA breaks, and its deficiency leads to Homologous recombination deficiency (#HRD), resulting in genomic instability and contributing to cancer.
HRD mutations, including #BRCA1 or #BRCA2 mutations are important actionable biomarkers in #Ovariancancer, that are sensitive to #PARP inhibitors that block the repair of #DNAdamage, such as #olaparib, #rucaparib, and #niraparib.

Patients with mutations in BRCA1/2 account for ~15% (range 7%–21%) of ovarian cancers. Several phase-III double blind, randomized trials have shown that patients with advanced ovarian cancer carrying BRCA1/2 mutations have better progression-free survival (PFS) with PARP inhibitors compared to placebo (SOLO-1 trial Olaparib, PAOLA-1 trial Olaparib + Bevacizumab, PRIMA trial Niraparib)

We sequenced 89 of our 1100+ Ovarian cancer resection cases using a 43-gene HRR #NGS panel, which identified several mutations in genes involved in HR pathway, such as TP53, BRCA1, ARID1A, BRCA2, PTEN, ATR and ATM. We identified pathogenic/likely pathogenic BRCA1/2 #missense and #truncated mutations (see figure below) that result in the loss of BRCA1/2 tumor suppressor function. These oncogenic alterations may predict response to PARP inhibitors and guide choice of therapy.

Today is World Ovarian Cancer Day

World Ovarian Cancer Day is observed on May 8th each year, to raise awareness about Ovarian Cancer, its symptoms, risk factors, and the importance of early detection and personalized treatment. Ovarian cancer is one of the most common gynecological cancers that ranks third after cervical and uterine cancer with high incidence in Asian women (9.2 per 100,000), with poor prognosis and high mortality rate.

In our biobank, we observe most ovarian cancer cases are detected at a young age with a median age of only 53 years, and in most cases cancer had already advanced and spread to both ovaries, bilateral cancer. If they had been detected earlier, they could have been cured as the cure rate for ovarian cancer is >80% if detected at early stage.

Epidemiology of ovarian cancer, June 2020
https://pdfs.semanticscholar.org/17c5/6233f2de1692f4b542db46bfec48e8090084.pdf

Assessment of DLL3 and CD3 Expression in Pediatric Tumor FFPE Samples for Potential DLL3-Targeted Immunotherapy

Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is a promising therapeutic target that is upregulated in Small Cell Lung Cancers (SCLC) and Neuroendocrine carcinomas but is not detectable in normal adult tissues. Various DLL3-specific therapies are under clinical development, including ADC rovalpituzumab tesirine (#Abbvie), bispecific TCE molecule AMG 757 (#Amgen), and CAR-T therapy AMG 119 (#Amgen), for the treatment of SCLC and neuroendocrine carcinomas.

We evaluated DLL3 expression in several tumor types, along with CD3, a marker for T-cell infiltration in tumors, to assess their potential for DLL3-targeted immunotherapeutic agents. DLL3 showed positive staining in neuroblastoma and pediatric tumors, such as Ewing’s sarcoma, osteosarcoma, rhabdoid tumors, Hodgkin’s lymphoma, rhabdomyosarcoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL).

The landscape of actionable genomic alterations in lung adenocarcinomas in India

Sapien Biosciences is excited to share our recently published article, titled “The Landscape of Actionable Genomic Alterations in Lung Adenocarcinomas in India,” in Frontiers in Genetics, section Genetics of Common and Rare Diseases.

Our retrospective study, involving 53 Indian Lung Adenocarcinoma patients and utilizing a targeted NGS panel of 46 cancer-relevant oncogenes, revealed pathogenic or likely pathogenic variants in 94% of cases. Notable findings include a high prevalence of TP53 (52.8%) and EGFR (50.9%) mutations, gender-based differences in genetic alterations, and the detection of clinically actionable variants in 79% of cases. These results emphasize the crucial role of NGS in uncovering actionable molecular alterations, enhancing our understanding of NSCLC’s molecular landscape, and facilitating personalized treatment for Indian patients based on their unique genetic profiles.

We extend our gratitude to the entire research team, collaborators @Thermo Fisher Scientific, @q-annie-hasan, @Dr Aruna Priya Kamireddy, and Frontiers in Genetics for helping us make this significant contribution to Indian genomics research possible.

Please find the link to our publication below:

https://www.frontiersin.org/articles/10.3389/fgene.2023.1256756/full

Timeline of Precision Medicine in Breast cancer

The timeline of breast cancer care and therapy is marked by significant milestones that have transformed patient outcomes and the way we approach this devastating disease as shown in the figure here. From the pioneering mastectomy procedures of the late 19th century to the development of targeted therapies specifically blocking the drivers of breast cancer such as ER, PR, HER2 personalized medicine has come a long way in recent years. The diagnosis and therapy guidance of breast cancer has evolved now to 4 major subtypes with personalized treatment strategies that are tailored to individual patient’s tumour characteristics and aggressiveness.

Breakthroughs in chemotherapy, hormonal therapy, most recently immunotherapy, along with advances in surgical techniques to preserve the breast tissue, and improvement in radiation therapy have all contributed to significant progress in breast cancer treatment. In the last 20 years, multiple treatment options have emerged for recurred and metastatic breast cancer. The effectiveness of such targeted treatments is higher and it has fewer side-effects, so it improves the quality of life. Simultaneously, awareness of risk factors including the role of BRCA1/BRCA2 genes have led to more women understanding hereditary risk and the need for regular screening.

In recent years, Next-Generation Sequencing (NGS) has been a pivotal player, enabling comprehensive genome analysis and uncovering rare genetic mutations that can be the targets of new drugs. These breakthroughs have ushered in an era of personalized medicine enhancing the overall quality of care as well as long-term survival in breast cancer.

Diagnostic methods for breast cancer used in India

Breast cancer can be diagnosed through multiple tests, including a mammogram, self-examination, ultrasound, MRI and biopsy. If the doctor finds an area of concern on a screening test (a mammogram), or if the patient has symptoms that could mean breast cancer, then more tests need to be done in order to diagnose whether it is cancer or not. The most common symptom of breast cancer is a new lump or mass. Breast cancer is sometimes found after symptoms appear, but many women with breast cancer have no symptoms. This is why regular breast cancer screening is so important. Any change in breast should be checked by a physician.

Most widely used methods of diagnosis are as follows:
1) Mammograms : low-dose x-rays
2) Ultrasound (USG) : sound waves and their echoes to make computer pictures of the inside of the breast. It can show certain breast changes, like fluid-filled cysts, that can be harder to see on mammograms.
3) MRI : radio waves and strong magnets to make detailed pictures of the inside of the breast.
4) Biopsy including Core needle biopsy, FNAC, or Surgical biopsy: this is done when mammograms, or another imaging test, or a physical exam shows a breast change that may be cancer.
A biopsy is the only way to know for sure if it’s cancer.

References:
Breast Cancer Mode of Detection in a Population-Based Cohort- 2022-

https://pubmed.ncbi.nlm.nih.gov/36737116

Tru-Cut Biopsy versus Fine Needle Aspiration Cytology in Diagnosis of Early Breast Cancer-2023 https://ijmpr.in/article/Tru-Cut+Biopsy+versus+Fine+Needle+Aspiration+Cytology+in+Diagnosis+of+Early+Breast+Cancer


Fine-needle aspiration cytology versus core needle lymph node biopsy in axillary staging of breast cancer – 2022 https://ejrnm.springeropen.com/articles/10.1186/s43055-022-00895-w
Comparison of ultrasound and mammography for early diagnosis of breast cancer among Chinese women with suspected breast lesions: A prospective trial – 2022
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663682/

Only a small minority of Breast Cancer Cases are currently Early Stage and Early Grade

As mentioned in our previous post, it is important to understand the Grade and Stage of #breastcancer to provide the best care for patients. Grade and Stage are linked to patient prognosis with Stage I cases having a >90% survival rate over 5 years.
At Sapien, we examined the Grade and Stage information available for our #biobank breast cancer cases. Grade was available for 6965 patients and Stage for 3415 patients, with missing information being filled in over time. Our distribution shows Grade 1 in only 9% cases, Grade 2 in 51%, and Grade 3 in 40% of cases. Stage II is the most prevalent at 55%, followed by Stage III at 28.4%, with early Stages 0 and I being only 13%. Our goal is to increase awareness of the importance of regular screening through breast self-examination and #mammograms to decrease cases being detected at later Grades and Stages.

Staging of Breast Cancer is Important

Advancements in #tumor biology and prognostic #biomarkers, such as the estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67, have empowered clinicians to understand why patients with similar stages have significantly different outcomes. The 8th edition of the American Joint Committee uses nine stages (0, IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV) based on anatomical staging, taking into account the extent of the primary tumor (T), the status of the regional lymph nodes (N), and metastasis (M), and incorporates biomarkers (histologic grade, ER, PR, HER2 expression, and multigene panels) into the traditional anatomical TNM staging. The higher the number, the more advanced the cancer is.
Staging allows for a more precise and accurate stratification of patients, impacting survival outcomes, with >90% survival over 5 years in Stage I breast cancer (from SEER database).

In addition to Stage, knowing the Grade of cancer is also important, to identify patients at risk for adverse outcomes who may be eligible for (neo)adjuvant therapies. There are three grades of malignancy (Grades 1-3), based upon the differentiation of tubule formation, pleomorphism, and “hyperchromatosis” or mitotic nuclei. The higher the number, the more aggressive the cancer is.

Simply put, Staging means how big the cancer is and whether it has spread. Grading means how abnormal the cancer cells and tissue look under a microscope.

Matched Plasma and Tumor blocks Available from Consented Cancer Patients

Sapien’s #biorepository is expanding with the collection of fresh blood from cancer patients prior to surgery, with informed consent. The collection covers all organs, including #Breastcancer (>320 cases). The blood is processed to #plasma and #PBMCs or cell pellets. Matched #FFPE tumor blocks are also available. With 6 sites now, the #biobank is growing rapidly to enable #cancer ‘omics.

A detailed questionnaire captures risk factors, social history, demographics, pathological diagnosis and biomarkers. Patients are followed up for treatment and 5-year outcomes with respect to response, recurrence or metastasis, and overall survival.
To know more, please visit www.sapienbio.co.in or write to queries@sapienbio.com