Know your subtype of breast cancer

Dr Ronwyn van Eeden explains the different subtypes of breast cancer and why treatment for each differs.

It’s important to remember that not all women diagnosed with breast cancer can be categorised or treated in the same way. Historically, breast cancer was referred to as a single disease, it’s now widely known that it’s a group of diseases that have different molecular subtypes (the genes that cause the cancer to grow) and histological subtypes (where the tissue originates from).

Distinguishing the subtype of breast cancer is important as it impacts treatment decisions immensely, such as whether or not patients need systemic therapies which include chemotherapy, targeted therapies, hormonal blockade and, more importantly, how to sequence these treatments.

Treatments also include different combinations of modalities with systemic therapy, such as surgery and radiation. The more aggressive molecular subtypes of cancers usually require neo-adjuvant chemotherapy (before surgery).

Each woman diagnosed with breast cancer follows a unique, niche treatment that is tailored for her as an individual (which is why it’s important not to compare your journey to anyone else’s). Different subtypes will respond to therapy in different ways.

Behaviour and prognosis of each subtype also varies, and they have different risk factors pertaining to potential for recurrence or metastases (spreading of the cancer to other sites in the body). Other prognostic factors to be considered also are the grade and stage of the cancer. There are three grades of cancer: grade 1 cancers usually behave more indolently whereas grade 3 cancers are more aggressive and grade 2 is somewhere in the middle. The more advanced the stage, for example, if there are lymph nodes involved, the higher the risk is. Treatment thus also differs depending on whether it’s an early-, advanced stage or metastatic breast cancer.

Histological subtypes

These are based on the size and shape and arrangement of the breast cancer cells. Most breast cancers (75%) are classed as no special type previously referred to as ductal carcinomas. The special subtypes include lobular cancer (15%) and other less common types include tubular, mucinous, cribriform and papillary carcinomas.

Molecular subtypes

These pertain to the different receptors or drivers for growth of the cancer. It’s mandatory that every woman who is diagnosed with breast cancer has the following immunohistochemical tests and receptors performed on the biopsy specimen to see which molecular subtype they belong to: oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) (a protein that promotes growth of cancer cells).

HER2 in a normal breast usually controls how healthy breast cells grow, divide and repairs itself. Excessive HER2 growth causes cells to grow too fast or abnormally and causes breast cancer.

Ki-67 is the final test done which is a nuclear protein associated with cellular proliferation, which tells how fast or slow cells grow and is also associated with prognosis.

Different molecular subtypes

Breast cancer is largely divided into the following molecular subtypes:

Hormone receptor (HR) positive and HER2 negative which is further subdivided into luminal A (those with low Ki-67) and luminal B (has high Ki-67) or if the PR is negative.

Luminal A is the most prevalent subtype, usually have a favourable prognosis, are slow-growing and respond well to hormonal therapy. Luminal B subtypes behave more aggressively and often require chemotherapy as part of treatment.

HR negative and HER2 negative cancers are referred to as triple-negative breast cancer or basal-like cancer and is one of the most aggressive subtypes and tend to have a risk for recurrence and distant metastases. These are almost exclusively treated with chemotherapy and in certain special instances, immunotherapy can be considered. Triple-negative breast cancers are more prevalent in patients who have a BRCA1 mutation, younger women and black women.

HER2 positive breast cancer can be HR negative or positive, they also tend to grow faster than luminal type cancers. These are usually treated with a combination of anti-HER2 therapy and chemotherapy. There are different types of anti-HER2 therapy which are utilised in different settings of this disease but is mandatory that an anti-HER2 agent is used as this greatly improves the prognosis of patients.

Molecular subtype	Receptors	Behaviour	Treatment	Incidence
Luminal A	HR+ HER2 – Low Ki-67 (usually < 14%)	Slow-growing	Hormonal blockade CDK 4/6 inhibitors in metastatic disease PIK3CA inhibitors	70% (Most common type)
Luminal B	HR+ HER2 – High Ki-67 (usually > 14%)	Faster growing	Hormonal blockade Chemotherapy CDK 4/6 inhibitors in metastatic disease PIK3CA inhibitors	10-20%
HER2 positive	HER2 + HR – or HR+ Varying Ki-67	Aggressive	HER2 targeted therapy Chemotherapy Hormonal therapy if HR+	10-15%
Triple-negative	HR – HER2 – Usually high Ki-67	Very aggressive	Chemotherapy Immunotherapy in special circumstances	15-20%

Breast cancer is the most prevalent cancer in women and understanding the molecular subtypes helps us to predict how the cancer cells will behave and has helped to develop guidelines and a standard of care for each subtype in order for women to have the best outcomes possible.

References

Resources for molecular subtypes of breast cancer:

MEET THE EXPERT – Dr Ronwyn van Eeden

Dr Ronwyn van Eeden is a medical oncologist in private practice in Rosebank, Gauteng. She is also an honorary consultant in oncology at the Chris Hani Baragwanath Academic Hospital.