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 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.

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.

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

Studies have shown that the risk for having breast cancer is due to a combination of factors. One of the main factors that influences the incidence of breast cancer is age, with the highest incidence rates being in older people. Most breast cancers are found in women who are 50 years or older.

The American Cancer Society (ACS) recommends mammograms for women at average risk as follows:
1) Age between 40 and 44 – option to start screening annually,
2) Age between 45 to 54 – mammogram recommended every year, and
3) Age between 55 and older – can switch to mammogram every other year, or continue annually.

Women who are at high risk for breast cancer (based on the risk factors of breast cancer posted on 5th October) should undergo a breast MRI and a mammogram every year, typically starting at age 30.

In the analysis of data from a sample size of 13,298 breast cancer cases from our biobank, we found that the mean age of the patients with breast cancer is 52, and the median is 56.

Detecting and diagnosing breast cancer early is the most effective way to reduce mortality rates. The emphasis on early detection of breast cancer is due to the significant impact it has on the survival rate. According to the ACS, the 5-year survival rates for localized breast cancer (cancer that has not spread beyond the breast) is 99%.

References:
Yedjou CG et al., Adv Exp Med Biol. 2019, Ho PJ et al., Genet Med. 2023, Kang SY et al., J Breast Cancer. 2021, Co M et al., Cancer Treat Res Commun. 2020, Sinha S et al., J Surg Res. 2022