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Biomarkers in Breast Cancer

Biomarkers in Breast Cancer

Biomarkers in Breast Cancer: Breast cancer is a complex heterogeneous group of tumors with diverse histological, clinicopathological features defined by unique molecular signatures. Breast cancer is the second leading cause of cancer death in women following lung cancer. Approximately 300,000 new cases of breast cancer are diagnosed every year in the United States. One in eight women has a lifetime probability of developing breast cancer.

Biomarkers in Breast Cancer targeted therapy was first introduced to treat breast cancer in 1970’s with the use of tamoxifen to treat estrogen receptor (ER) positive tumors. Currently, clinically actionable genomic abnormalities with FDA approved drugs include alterations in the following genes: ERBB2, ER, PR, BRCA1, BRCA2, PIK3CA.

Biomarkers in Breast Cancer Patients

ERBB2 (HER2) amplification/over expression:

Twenty percent of breast tumors have overexpression of the epidermal growth factor receptor 2 (ERBB2 or HER2). Breast tumors with ERBB2 amplification is commonly referred to as HER2 positive tumors. ERBB2 amplification lead to increased cell proliferation triggering cancer growth. HER2 status of a breast tumor can be assessed by immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH) or next generations sequencing (NGS). While HER2 positive breast tumors are considered aggressive, they can be treated with HER2 inhibitors including trastuzumab, ado-trastuzumab, pertuzumab, neratinib, and lapatinib. The first HER2 inhibitor trastuzumab was approved in 1998 signaling a paradigm shift of treating these tumors.

ER/PR overexpression:

Approximately 80% of breast cancers have estrogen receptor (ER) expressed in cancer cells and 65% of breast tumors have progesterone receptor (PR) expressed. If one or both receptors are expressed in the cancer cell, the tumor is referred to as hormone receptor positive breast cancer. ER and PR positive breast cancer cells utilize naturally occurring hormones estrogen and progesterone to sustain cancer growth. These tumors can be treated with hormone (endocrine) therapy drugs including anti-estrogen drugs and aromatase inhibitors. Anti-estrogen drugs such as tamoxifen and fulvestrant prevent the hormones from attaching to the receptors (ER and PR) in the cancer cell. Aromatase inhibitors including anastrozole, letrozole and exemestane reduce the production of estrogen in the body. Hormone positive breast cancer patients generally have better disease prognosis.

BRCA1/BRCA2 mutations:

BRCA1 and BRCA2 mutations predisposes patients to develop breast cancers. BRCA1 and BRCA2 mutations can be inherited (germline mutations) or acquired during the lifetime (somatic mutations). 3% of the breast tumors occur due to germline mutations in BRCA1 or BRCA2. One study estimated that approximately 70% of women with either BRCA1 or BRCA2 mutations will develop breast cancer by the age of 80. Women of Ashkenazi Jewish descent has been reported to have a higher prevalence of BRCA mutations compared to the rest of the US population. BRCA1or BRCA2 positive breast tumors are often negative for estrogen receptor (ER) and HER2. BRCA mutated breast tumors can be treated with PARP inhibitors. The FDA has approved olaparib and talazoparib to treat metastatic HER2 negative breast tumors with an inherited BRCA1 or BRCA2 mutations.

Cancer Biomarkers

PIK3CA mutations:

PIK3CA mutations are found in approximately 30% of breast tumors. Mutations in PIK3CA leads to enhanced cell signaling initiating tumorigenesis. The majority of PIK3CA mutations are located in two “hot spots”: E542K or E545K in exon 9, and H1047R or H1047L in exon 20 The FDA has approved alpelisib, a targeted PIK3CA inhibitor for HER2 negative breast cancers with a PIK3CA mutation. A clinical trial reported that PIK3CA mutated breast cancer patients on alpelisib show an average of 11 months progression free survival compared to 5.5 month progression free survival without alpelisib.

FGFR alterations:

FGFR family has 4 receptors: FGFR1, FGFR2, FGFR3, and FGFR4 that are often mutated or amplified in breast cancer. Aberrant activation of the FGFR pathway leads to cell proliferation and promote tumor formation. While FGFR inhibitors are not yet approved by the FDA for breast cancer, numerous late stage clinical trials are evaluating their efficacy and safety in FGFR altered breast tumors.


  • Malthe says:

    Do you help patients in Denmak? My grandma has breast cancer stage 3. Do we need to travel to US?

    • Fiona Evans says:

      Hello Malthe, Thank you for reaching out, we help patients all over the world. We offer our Virtual Tumor Board and Clinical Trial Matching System to patients in and outside the US. With either of these services, patients are able to stay where they are and utilize our services, no travel needed. We are available by live chat, email at, and by phone at 844-627-7246.

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