The management of early breast cancer has evolved immensely over the past few years, particularly in patients with hormone receptor positive (HR+) and HER2 negative (HER2-) cancers. Dr Ronwyn van Eeden tells us more.
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Early breast cancer refers to cancer that hasn’t spread beyond the breast and regional lymph nodes.
HR+ and HER2- cancers refer to patients who have positive receptors for oestrogen and progesterone and are HER2 negative.
Most early breast cancers have an excellent five-year survival rate, with some Stage 1 cancers having a 99% survival rate. Though as the stage increases, the risk of recurrence, both local (within breast and lymph nodes) and distant (bone, lung, or liver) also increases.
There are additional features or characteristics of early receptor HR+ HER2– breast cancer that can infer a higher risk.
High-risk patients include those with:
• Large tumours
– Usually T3 – size > 5cm or more.
• Positive lymph nodes
– The higher number of positive lymph nodes increases the risk of recurrence.
• High grade cancers
– Low grade (grade 1) usually means the cancer is slow-growing and less likely to spread and high grade (grade 3) means a fast-growing cancer that’s more likely to spread. An intermediate grade (grade 2) means the cancer is growing faster than a grade1 but slower than a grade 3.
• High Ki-67
– A nuclear protein used to evaluate proliferation of cells or how quickly cells divide.
– Different cut-offs for this value can be used with > 20% indicating a more aggressive cancer.
In some circumstances, oncologists can also use specific genomic testing which can scientifically predict the risk of recurrence in HR+ HER2- breast cancer, such as Oncotype DX or MammaPrint.
These tests also help make decisions regarding whether a patient with early HR+ HER2- breast cancer, with or without positive nodes, would benefit from adjuvant chemotherapy (chemotherapy after surgery).
Treatment
Some early HR+ HER2- breast cancers may also need neoadjuvant chemotherapy (chemotherapy before surgery). This is in patients with high risk or high grade tumours that are too large to operate on upfront, or if the nodal burden is high.
All decisions about whether patients need surgery or other neoadjuvant treatments first must be made in a multi-disciplinary team.
However, it’s important to note that most HR+ HER2- breast cancers don’t require chemotherapy. These are usually treated adequately with endocrine therapy in the neoadjuvant or adjuvant setting.
Endocrine therapy
This blocks or lowers the levels of oestrogen and progesterone that promote breast cancer growth.
There are different types of endocrine therapies and the choice of therapy is usually determined by the menopausal status and risk profile of the patient, and possible side effect profile.
Types of endocrine therapy include:
- Selective oestrogen receptor modulators (SERMs), such as tamoxifen which prevent oestrogen from binding to receptors that stimulate growth.
- Aromatase inhibitors (AIs) which reduce the production of oestrogen in the body by blocking an enzyme called aromatase. Examples are letrozole, anastrozole, or exemestane.
- Ovarian suppression in pre-menopausal females is usually in the form of an injection called goserelin.
- Newer endocrine therapies are also in development and can be available on clinical trials. Patients should always enquire if there are any clinical trials available for the type of breast cancer they have. This allows access for innovative therapies.
All patients with invasive HR+ HER2- breast cancer should receive endocrine therapy for a duration of five to 10 years after their surgery, depending on the risk of their cancer.
Cyclin-dependent kinases (CDKs)
The new addition in the treatment of HR+ HER2- breast cancer is the inclusion of new drugs: CDK inhibitors. This would be in the adjuvant setting in combination with endocrine therapy for patients with high-risk disease.
These drugs work by playing a crucial role in controlling the cell cycle which governs cancer growth.
They can be given for two to three years in combination with endocrine therapy to decrease the risk of cancer recurrences even further.
Currently, there is only one CDK drug registered in SA for use in this setting; with a second drug waiting for registration approval. These two drugs differ slightly in their indications and also in side effect profile and need to be selected carefully per patient.
BRCA1 and BRCA2
High-risk HR+ HER2- early breast cancer patients who carry a hereditary cause of breast cancer, such as genes involved in DNA damage repair, namely BRCA1 and BRCA 2, may also benefit from the addition of a drug called a PARP inhibitor which specifically blocks this abnormality in the adjuvant setting.
The landscape of optimising treatment
The landscape of therapies for early HR+ HER2- is changing rapidly; there has been a move towards identifying patients at higher risks for recurrences to add beneficial therapies which further decrease this risk. These are promising and give even more hope to improve survival and outcomes for this subgroup of patients where better options were previously lacking.
MEET THE EXPERT – Dr Ronwyn van Eeden
Dr Ronwyn van Eeden is a medical oncologist in private practice in Rosebank, Gauteng. She has a special interest in breast cancer, lung cancer, and precision oncology.
Header image by Freepik
