Diagnosis, Treatment and Prognosis of HER2 Positive Breast Cancer

How do you Diagnose HER2 Positive Breast Cancer?

HER2-positive breast cancer can be diagnosed by the following four immunological techniques, highlighted below:

• Immunohistochemistry (IHC): This technique is used for detecting antigens within cells of tissue sections by exploiting the property of antibodies to bind specifically to antigens in biological tissues. The IHC test determines the level of HER2 protein within the cancer cells. The results may be 0 (negative), 1+ (also negative), 2+ (borderline), or 3+ (positive i.e. HER2 protein overexpression).
• Fluorescence in situ Hybridization (FISH): This is a molecular cytogenetic technique that uses fluorescent probes to ‘map’ the genetic material in cells. The fluorescent probes bind to those areas of the chromosomes that have a high level of sequence similarity and help to visualize specific genes or parts thereof. The FISH test detects whether there are too many copies of the HER2 gene in the cancer cells. The test may be negative (no HER2 gene amplification) or positive (HER2 gene amplification).

• SPOT-Light^® HER2 CISH: This technique is known as subtraction probe technology chromogenic in situ hybridization (SPOT-CISH). The test uses the SPOT-Light^® HER2 CISH kit manufactured by Invitrogen, California, USA. The test quantitatively determines HER2 gene amplification in breast cancer tissue sections using a combination of chromogenic in situ hybridization (CISH) and brightfield microscopy. The test detects whether there are too many copies of the HER2 gene in the cancer cells. The test may be negative (no HER2 gene amplification) or positive (HER2 gene amplification). This test is recommended for patients in whom Herceptin^® (trastuzumab) treatment is being considered.
• INFORM HER2 Dual ISH: This test uses the INFORM HER2 Dual ISH DNA Probe Cocktail manufactured by Roche, Basel, Switzerland. This technique determines the HER2 gene status by enumeration of the ratio of the HER2 gene to Chromosome 17. The HER2 and Chromosome 17 probes are detected using two (dual) color CISH on human breast cancer tissue specimens followed by light microscopy. The test detects whether there are too many copies of the HER2 gene in the cancer cells. The test may be negative (no HER2 gene amplification) or positive (HER2 gene amplification).

What are the Treatment Options for HER2 Positive Breast Cancer?

Treatment of HER2-positive breast cancer primarily involves targeted strategies using monoclonal antibodies (mAb) and newer chemotherapeutic agents that target the HER2 protein. The following drugs are recommended for the targeted therapy of HER2-positive breast cancer:

• Trastuzumab: This is a mAb used to treat HER2-positive breast cancer and is sold under the brand name Herceptin^®. The drug can be used for early-stage HER2-positive breast cancer that may or may not have spread to the lymph nodes. It can be used alone or in combination with other drugs used for chemotherapy.
• Ado-Trastuzumab Emtansine (T-DM1): This is an antibody-drug conjugate, consisting of the mAb trastuzumab and the cytotoxic drug DM1. It is sold under the brand name Kadcyla^®. This drug is approved for treatment of HER2-positive breast cancer that has spread to other parts of the body (metastatic breast cancer) after prior treatment with Herceptin^®.
• Pertuzumab: This is a mAb used in combination with Herceptin^® and the chemotherapeutic drug docetaxel for the treatment of patients with early-stage HER2-positive breast cancer who are at a high risk of recurrence. Pertuzumab is sold under the brand name Perjeta^®.
• Lapatinib: This is a class of anticancer drugs known as dual tyrosine kinase inhibitors that block the HER2 and epidermal growth factor receptor pathways and is sold under the brand name Tykerb^®. It is used in combination with a drug called capecitabine for the treatment of metastatic HER2-positive breast cancer in patients who received prior therapy with other chemotherapeutic drugs, including anthracycline, taxane, and Herceptin^®.
• Neratinib: This drug is sold under the brand name Nerlynx^®. It is a once-daily oral anticancer drug for patients who have just finished Herceptin^® therapy following surgery for early-stage HER2-positive breast cancer.

Other treatments that are sometimes recommended include surgery and radiotherapy, but these are less effective for treating HER2-positive breast cancer.

What is the Prognosis of HER2 Positive Breast Cancer?

The prognosis or outlook for patients with HER2-positive breast cancer depends on the stage of the cancer. In general, the prognosis is better for patients if the cancer is detected at an early stage as opposed to a later stage, when it is most likely to have spread to other areas of the body. However, the prognosis can vary from person to person, depending on their individual situation or circumstance. Moreover, with the advent of targeted therapies based on mAb and newer chemotherapeutic drugs, as well as their combinations, the prognosis has become much better.