Posted on Dec 06, 2022

Breast cancer tissue is assessed at diagnosis to determine treatment approach and prognosis. Whilst stage 4 or metastatic breast cancer is classed as incurable, treatment options that can prolong life are becoming available. However, we need to ensure that diagnostic technology used in labs keeps pace with advances in treatment, so that those with this late-stage cancer can access these innovative therapies.

What is stage 4 breast cancer?

Stage 4 breast cancer is also known as metastatic breast cancer, secondary breast cancer or advanced breast cancer.

All these terms cover cases where the cancer has metastasized from the breast to other regions of the body. Most commonly the lymph nodes, bone, liver, lungs and brain. Signs of metastatic breast cancer depend on the site of spread.

How common is stage 4 breast cancer?

In terms of stage 4 breast cancer rates, the charity Breast Cancer Now states that around 35,000 people are living with this advanced diagnosis in the UK. Approximately 5% of women are diagnosed with  stage 4 breast cancer at the start of their treatment journey.

Unfortunately, once the cancer has metastasized it is incurable: in Europe the 5-year survival rate is in the range of 38% (ESMO, 2021). As of 2018, metastatic breast cancer was the leading cause of death from all cancers in women, accounting for 3.6% of all deaths..

That is why it’s vital that there is a focus on better treatments as well as improved diagnostic pathways to enhance outcomes.

Treatment advancements in stage 4 breast cancer

Therapy options for stage 4 breast cancer depend on assessment of tumour biomarkers, as well as sites of metastasis. Treatment approaches typically include endocrine therapy, chemotherapy, biological therapies as well as palliative treatments for example, targeting spread to the bone. Some sub-types of metastatic breast cancer have been historically harder to treat such as low HER2 and triple-negative breast cancers.

Anyone involved in the breast cancer world will know that there have been many positive developments made in treatment of all subtypes of metastatic breast cancer - leading to improvements for women living with the disease.

Research activity is ongoing, and there are hopes that combination strategies may be particularly effective, such as CDK 4/6 inhibitor alongside immunotherapy, oral selective estrogen receptor degraders (SERDS) or HER2 inhibitors. In addition, several new antibody-drug conjugates (ADC) are currently being explored and developed.

Treatment of HER2-low breast cancer

Further definition of breast cancer sub-types has also meant improved targeted treatments for those with metastatic disease.

HER2-low accounts for more than half of all metastatic breast cancers. Traditionally HER2‑low breast cancer was treated as HER2-negative and had limited therapy options.

However, the recently published results of the DESTINY-Breast04 trial clinical trial, of trastuzumab deruxtecan (Enhertu) showed improved survival of those with HER2-low metastatic breast cancer, when compared with chemotherapy. A significant clinical development for this cohort of patients.

Researchers are exploring other targeted therapies for HER2-low breast cancer. But recent papers identify that breast cancer subtype classification needs rethinking and HER2 expression levels must be better identified to guide treatment. They highlight the low accuracy of IHC/ISH assays.

Quantitative analysis techniques such as MammaTyper® offer advantages for an improved accuracy of sub-typing, so that those facing metastatic breast cancer can access treatments that will offer hope.

MammaTyper® allows pathologists to amplify, detect and quantify the mRNA expression status of ERBB2 (HER2), ESR1 (ER), PGR (PR) and MKI67 (marker of proliferation Ki-67) to subtype breast cancer appropriately and accurately in patients (as recommended by St Gallen, 2013 and subsequent updates).

Thanks to the COVID-19 pandemic, most laboratories have the equipment to read RT q-PCR results as the assay is certified for use with industry-standard RT q-PCR machines.

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