Metastatic HER2-Positive Breast Cancer Landscape: What You Need to Know

Breast cancer is not a single disease leading to abnormal cell division in breast tissues. Breast cancer is the most common form of cancer in women. Each year, it affects over 2 million women globally and is the most significant cause of death among women.  According to DelveInsight’s estimates, there were around 297K new cases of female breast cancer in the United States in 2023.

Based on the menopausal status of women suffering from breast cancer, in the US, a higher number of cases were observed for the postmenopausal Breast cancer, accounting for 80–20% of the cases, while premenopausal women contributed a significantly lesser proportion of the patients.

Metastatic HER2-Positive Breast Cancer

Metastatic HER2-Positive Breast Cancer is a type of breast cancer where biopsy tests of the cancerous cells show a positive status for a protein receptor called human epidermal growth factor receptor 2 (HER2). This receptor protein, when functioning normally, regulates the healthy division and growth of breast cells. In HER2-positive breast cancer, the cancer cells have an overexpression of the HER2 protein, leading to rapid and uncontrolled cell growth. This aggressive form of cancer often spreads to other parts of the body, making it more challenging to treat.

Metastatic HER2-Positive Breast Cancer Symptoms

Like many types of breast cancer, Metastatic HER2-Positive Breast Cancer symptoms may not be immediately obvious. When they do manifest, they can include changes in the size, shape, or contour of the breast; the presence of a mass or lump as small as a pea; a persistent lump or thickening in the breast or underarm area; alterations in the skin’s appearance on the breast or nipple, such as dimpling, puckering, scaling, inflammation, or discoloration; a marble-like hardened area under the skin; and discharge from the nipple that is either blood-stained or clear.

Diagnosis of Metastatic HER2-Positive Breast Cancer

Healthcare providers diagnose all breast cancers, including Metastatic HER2-Positive Breast Cancer, with breast biopsies. If these biopsies reveal cancer, a medical pathologist will examine the breast tissue cells for signs of HER2 proteins using laboratory tests, crucial for breast cancer diagnosis. The immunohistochemistry (IHC) test, which uses immunostaining to detect HER2 protein levels in cancerous cells, is a common method. To confirm IHC test results, pathologists may employ fluorescence in situ hybridization (FISH), a test that identifies extra copies of the HER2 gene. If lab tests indicate normal HER2 protein or gene levels, the breast cancer is classified as HER2-negative. Conversely, high levels of HER2 proteins or genes signify HER2-positive breast cancer.

Pathologists further categorize this cancer subtype using a scoring system based on the HER2 protein levels in a breast tissue sample. For example, a score of 0 or 1+ indicates low levels of HER2 protein and a negative classification. A score of 2+ suggests moderate levels, prompting additional FISH testing to confirm results. A score of 3+ indicates many cancerous cells with high protein levels, classifying the sample as positive. This comprehensive approach ensures accurate breast cancer diagnosis and appropriate treatment planning for Metastatic HER2-Positive Breast Cancer.

What is the Metastatic HER2-Positive Breast Cancer Prevalence?

According to the World Health Organization (WHO), breast cancer resulted in 670K deaths worldwide in 2022. According to DelveInsight’s estimates, the total incident population of HER2-positive breast cancer in the seven major markets was nearly 102K cases in 2023. The cases in the 7MM are expected to increase during the forecast period, i.e., 2024–2034. The HR+/HER2+ breast cases were highest in the United States, accounting for ~32K cases. According to the estimates, most cases of HER2-positive breast cancer occur in people between 40 and 60 in the United States, accounting for ~52% of total cases in 2023. Among EU4 and the UK, Germany had the maximum total incident cases of HER2-positive breast cancer, with ~11K cases in 2023, while Spain accounted for the least number of cases. In Japan, stage-specific cases of HER2-positive breast cancer were highest in Stage II, accounting for ~6K cases in 2023. The Metastatic HER2-positive breast Cancer prevalence indicates a significant impact on healthcare systems across these regions.

Metastatic HER2-Positive Breast Cancer Therapy Landscape

The Metastatic HER-2 Positive Breast Cancer Market comprises a variety of treatment options, which are mainly categorized into pharmacological and non-pharmacological therapies.

Although the first-line treatment of metastatic breast cancer is mainly dependent on the receptor status, both estrogen and progesterone receptor status and HER2 receptor status should be tested.

Numerous treatment options for HER2-positive breast cancer are available, spanning both pharmacological and nonpharmacological categories. Recent advancements in HER2 treatments have improved the management of HER2-positive breast cancer, yet relapse remains a significant challenge due to disease heterogeneity and drug resistance mechanisms.

Traditionally, patients with metastatic HER2+ breast cancer were treated with conventional chemotherapy regimens until the advent of trastuzumab. In response to the rise of biosimilars, Roche introduced a subcutaneous (SC) formulation of HERCEPTIN in the EU in 2013 and the US in 2019, even with biosimilars available. Continuing to expand its HER2 franchise, Roche’s first ADC, KADCYLA, received FDA approval in 2013 for treating HER2-positive metastatic breast cancer following prior treatment with HERCEPTIN and chemotherapy. The second ADC to gain FDA and EMA approval is ENHERTU (trastuzumab deruxtecan), potentially revolutionizing the second-line treatment landscape and serving as a significant breakthrough for AstraZeneca and Daiichi.

An emerging therapy, SYD985, is making strides in this competitive landscape, including filing a Biologics License Application (BLA) in the US and EU. Several companies, such as Pfizer, Roche, Spectrum Pharmaceuticals, Hoffmann-La Roche, Eli Lilly and Company, and Ambrx, are actively engaged in mid- and late-stage research and development for HER2-positive breast cancer.

Metastatic HER2-Positive Breast Cancer Pipeline

The metastatic HER2-positive breast cancer pipeline is marked by a promising array of potential therapeutics despite its currently limited options. Companies like Byondis (SYD985), Roche (Giredestrant), Ambrx (ARX788), and Zymeworks/Jazz Pharmaceuticals (Zanidatamab) are leading mid- and late-stage research efforts in this field. ARX788, an anti-HER2 antibody-drug conjugate (ADC) from Ambrx, is undergoing Phase II trials and has demonstrated a favorable safety profile and preliminary efficacy in heavily pre-treated HER2-positive breast cancer patients. Zanidatamab zovodotin, developed by Zymeworks/Jazz Pharmaceuticals, combines a HER2-targeted bispecific ADC with a proprietary cytotoxic agent and is currently being evaluated in Phase II trials. Recent data from the Phase IIa trial presented at the San Antonio Breast Cancer Symposium (SABCS) 2023 highlights its manageable safety profile and effectiveness in HR+/HER2+ metastatic breast cancer.

Roche’s Giredestrant (RG6171, GDC-9545) represents a novel approach as a selective estrogen receptor degrader (SERD), which targets estrogen receptors to enhance degradation. This drug is in a Phase III trial, combined with PHESGO, for first-line maintenance in HR+/HER2+ breast cancer. With expectations for future filing in 2026 and beyond, Giredestrant underscores the optimistic outlook for advancements in the metastatic HER2-positive breast cancer therapeutics market.

Conclusion

The landscape of metastatic HER2-positive breast cancer treatment and research is rapidly evolving, with numerous advancements and promising therapies on the horizon. The increasing incidence of this aggressive cancer underscores the urgent need for innovative treatments that can address the challenges of disease heterogeneity and drug resistance. The introduction of targeted therapies, like trastuzumab, pertuzumab, and newer ADCs, such as KADCYLA and ENHERTU, has significantly improved patient outcomes. The ongoing development of novel therapeutics and the active engagement of key players in the field highlights a robust pipeline poised to bring forth breakthroughs in metastatic HER2-positive breast cancer management. As research progresses, the future holds promise for more effective and personalized treatment options, aiming to enhance the quality of life and survival rates for patients battling this challenging disease.