Why chemotherapy in early breast cancer?

In hope of clearing up the misconception that if a very small cancer is detected and removed surgically, no further treatment is needed, Dr Ronwyn van Eeden talks about treating early small breast cancer with chemotherapy and targeted therapy.

Early breast cancer is defined as stage one or stage two disease. When breast cancer is detected in early stages, we have the best chance at cure. Screening – checking for cancer with routine mammograms and self-examination – and early detection is the key to survival.

Curing breast cancer includes a multi-modality treatment, combinations of surgery, chemotherapy, endocrine therapy and radiation, and requires a multi-disciplinary team of surgeons, medical and radiation oncologists as well as psychologists, dietitians, genetic counsellors and other medical professionals that contribute to mentally healing and physically curing a breast cancer patient.

So the earlier and smaller, the better? Right? Right, but…the question often asked is: “If the breast cancer is detected early and is small, then surgically removed, why is further treatment needed?

Breast cancer has different subtypes and different cancer biology. The decision to treat is not made on the size alone, but on the characteristics of the cancer. Breast cancer carries different types of receptors. Receptors are drivers, found on the cancer, that causes it to grow, and are also used as targets for treatment. Breast cancer can have hormone receptors – oestrogen and progesterone, or a receptor called HER2, which is an abnormal gene that tends to be associated with more aggressive disease. When breast cancer has none of these receptors, it is called triple-negative breast cancer; this is also very aggressive and more difficult to treat, as there are no receptors to block, and in these cases, chemotherapy is always used. Another parameter looked at is called Ki-67 – this is a proliferation index and tells us how fast a breast cancer grows. When this index is high, the cancer tends to be fast-growing and chemotherapy is more likely to be used.

The nature of the disease – the grade, its receptors, how fast it grows and its likelihood to spread or recur – are the facts oncologists use to decide what treatment needs to be given after the cancer has been surgically removed.

When treating early breast cancer after surgery, the oncologist has many decisions to make: whether or not the patient needs additional scans to see if the cancer has spread, educating the patient on what therapies would benefit them, and, most importantly, how to decrease their risk of recurrence or metastasis, and minimise this risk at all costs.

When treatment is given for breast cancer after surgery, the term adjuvant therapy is used. This refers to either systemic (chemotherapy given intravenously or orally that goes through the entire body to kill cancer cells), targeted therapy (such as anti-HER2 therapy), or endocrine therapy (anti-hormonal treatment).

Certain types of breast cancer such as hormone receptor positive breast cancer with a high Ki-67 score will need chemotherapy in combination with endocrine therapy after surgery, as it is more aggressive. In the case of HER2 positive breast cancer, a combination of chemotherapy and a targeted anti-HER2 drug, called Herceptin, is used. As before mentioned, triple-negative breast cancer also warrants chemotherapy as it is aggressive.

In certain cases, radiation is also used after surgery, especially in cases where breast-conserving surgery is used or when lymph nodes are involved. The aim of this is to prevent the risk of recurrence or metastasis after initial surgery. The selection and choice to use adjuvant therapy is based on prognostic (how long a patient will live) and predictive (how the cancer behaves and what the chance of it coming back is) risk factors.

At times, however, the answer is not always clear-cut; some patients with hormone receptor positive disease, HER2 negative and low Ki-67 scores don’t always need chemotherapy. They might be candidates for endocrine therapy only. Different tools can be used, when oncologists see a patient after surgery, to decide whether or not they need only endocrine therapy or chemotherapy as well.

In the case of this subtype only, which is low-grade hormone receptor positive cancer, a test, called the Oncotype DX, is used. This test analyses a group of genes that can predict how a cancer is likely to behave and respond to treatment. Oncologists use the Oncotype result to help them decide what the patient’s risk is of breast cancer coming back, as well as how likely she is to benefit from chemo after surgery. The test results can come back low-risk, which means it is usually safe to use endocrine therapy only. If it shows intermediate to high-risk disease, chemotherapy will be prescribed as the risk of recurrence is much higher.

The downside of the Oncotype test is it is expensive, so many patients can’t afford to pay for it themselves, and many medical aids decline to pay for it based on the cost. Oncologists can use other tools and models online; these also calculate the risk of recurrence, and can be used if it is not possible to do the Oncotype DX.

Return of cancer locally, in the breast or spread distantly to other organs like the liver, lung, bones and brain, is common if surgery alone is used as the only modality of treatment. This is why adjuvant therapy is important.

In some very selective cases, even though the cancer is in an early stage  or small, the administration of chemotherapy or targeted therapy can be used before surgery. This is referred to as neo-adjuvant therapy and is often used when the initial biopsy shows a very aggressive cancer, such as triple-negative or HER2 positive breast cancers.

The aim, in these cases, is to try    and achieve a pathological complete response, meaning that after initial chemo or Herceptin is given, and then surgery is complete, there is no detectable cancer cells when the pathologist looks at the specimen. There is evidence to suggest that this correlates with a longer survival – you live longer and are less likely to have recurrence.

In the case of HER2 positive breast cancer, Herceptin would still continue adjuvantly for another year after initial treatment, as clinical trials show that in this type of aggressive cancer, patients that carry on with treatment for a year after live the longest.

If the nature of the cancer is aggressive, size really doesn’t matter, and the therapy should match the disease. There can be circulating cancer cells that have the potential to spread and cause the breast cancer to return.

When patients with early breast cancers are referred to me, I find this misconception to be dominant. The fear and anxiety of chemotherapy is overwhelming. Denial plays a big role in coming to terms with what has happened. The struggle of dealing with an unexpected diagnosis is real, on top of that having to deal with the difficulty of surgery, and then still needing additional therapy. It seems a huge mountain to face. The reality is that breast cancer has a greater ability to return, if it is not treated aggressively and optimally from the beginning.

Early diagnosis is when breast cancer has the most potential to be cured, and when there is a team of specialists on your side, with your best interest at heart, making sure you have the best treatment options available to you, you become a survivor.

My patient, Romy, (read her story on the next page) made me even more aware of this. She was very angry and perplexed on the day she met me; even after she had removed both breasts, I had the audacity to suggest she needed further treatment. She felt that she didn’t have cancer anymore, so why would I want to poison her with chemotherapy, and one whole year of Herceptin? And not even with a 100% guarantee! All I saw in front of me was a beautiful young woman, with the desire to live. I needed to treat Romy according to her tumour biology – the aggressiveness of its nature. Because I too wanted her to live.

It is not the size of the cancer that matters or what obstacles you encounter until the end of your treatment. You need to focus on the end result. The long-term goal is survival, and that is also the goal of adjuvant therapy.

MEET THE EXPERT

Dr Ronwyn van Eeden is a medical oncologist at the Medical Oncology Centre of Rosebank. She has a special interest in supportive care in cancer and new anticancer agents, especially immunotherapy.

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