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Positive Prognosis

UK researchers have identified a molecule that may help to fight ‘triple-negative’ breast cancer, writes Louise Ferreira.
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An increased awareness of breast cancer means more conversations are happening around diagnosis and treatment. And it seems one potential new treatment holds promise for patients who are resistant to chemotherapy: London researchers have identified a molecule that influences the behaviour of the dreaded “triple-negative” breast cancer.

But first, we need to understand the differences between cancers and how medical teams decide which treatment option is best for any one patient.

“I am often asked by my patients why Jane had chemo and radiation, why Sue had radiation only, and why Nomsa had a bilateral mastectomy and her sister had a breast-saving operation,” says Dr Carol Ann Benn, breast-cancer specialist.

Until a decade or two ago, breast cancers were classified and treated mainly according to size, which meant that tumours over a certain size would almost always require a mastectomy. Size also determined whether a patient would receive chemotherapy and radiation.

Then age became a determining factor. “Young people got chemo; menopausal women did not,” says Benn. “Finally, we recognised that it is actually about understanding the behaviour of tumours.”

This refers to the rate of growth, as well as to what Benn calls the “personality” of the cancer – that is, the type.

“‘Triple-negative’ cancer means the tumour is not hormone-sensitive,” she explains. During a biopsy, breast tumour tissue is tested for different hormone receptors, which indicate sensitivity.

“Three important receptors that you should know about are the oestrogen receptor (ER), the progesterone receptor (PR) and the Her 2 receptor,” says Benn. “If your cancer is ER and PR-positive, your oncologist will advise you on some form of endocrine treatment. There are many available, and usually after discussion in an MDM (multi-disciplinary meeting), one will be recommended by your oncologist.

“Endocrine therapy is chronic treatment, and usually starts after all other treatment is finished, and will need to be taken for at least five years, usually up to 10,” she adds.

It is critical that the test for the Her 2 receptor is carried out during a core biopsy, and if results are negative, that the final tumour specimen is tested again, says Benn.

Almost all cancers that are Her 2-positive will be treated with the drug Herceptin, and Herceptin is given with chemotherapy, as a general rule.

“All the above factors play a role in not only what the cancer looks like, but how it behaves,” says Benn. “The most important determinants of behaviour are the division rate and the receptors.”

Depending on its hormone sensitivity, breast cancer can be classified into one of four categories.

Luminal A cancer is ER and PR-positive, and is slow-growing. Luminal B cancer is also ER and PR-positive, but grows faster. “Most cancers can fit into this general category,” explains Benn.

Both Luminal A and B are Her 2-negative, while Her 2-positive cancers can be either ER and PR-positive or negative.

The fourth type of cancer tests negative to all three hormone receptors, and this is the dreaded “triple-negative” cancer. Triple-negative tends to be viewed more fearfully, since it can be more aggressive than the other types, often has a poorer prognosis and is more common among younger patients.

But if that’s the diagnosis you receive, don’t panic. “They can have a low or high division rate, and care should be taken not to take this entire group of baddies and lump them together,” adds Benn.

“Most [cancers], except the very small and the very sleepy, will probably need chemotherapy.”

It’s in the treatment of triple-negative that researchers have discovered a potential breakthrough. According to a press release from the Institute of Cancer Research in the UK, scientists have identified a molecule called PIM1, involved in “driving and controlling triple-negative breast cancers”.

PIM1 influences the “death threshold” of cancer cells targeted by chemotherapy, and the research teams have discovered that the molecule “has been hijacked and is being overproduced in the majority of triple-negative breast cancers”. This helps them to survive “by making them more resistant to the ‘death signals’ prompted by chemotherapy”, and explains why a large number of these cancers are aggressive and resistant to chemotherapy.

While PIM1 has little effect on normal cells, triple-negative cancers become “addicted” to it, suggesting that PIM1 inhibitors could be used to target cancer cells and make them more sensitive to other forms of treatment.

Benn points out that cancer treatment is not just about the tumour, but the individual person – their general health, as well as their body’s ability to fight disease and manage treatment.

Two other new fields of cancer treatment are immunotherapy and what is known as “basket oncology”. The latter is related to genetic profiling, suggesting that the appearance of the tumour and where it is found in the body are less important than its genetic makeup. This would allow oncologists to choose the best treatment option for the cancer, depending on its genetics.

“The frontier of cancer genetic profiling has expanded. We can study the sensitivity of cancers to certain drugs and whether certain chemo combinations may be more effective than others by understanding the genetic profiling of the cancer cell. This has resulted in more personalised cancer care.”

Immunotherapy uses your own immune system to fight diseases such as cancer, by stimulating it to work harder. “Other drugs help train the immune system to attack cancer cells specifically,” explains Benn.

Breast exam

All breasts are shaped differently, and one breast is usually larger than the other. Know the feel of your breasts; some feel fatty, some smooth, some lumpy. It’s important that you can recognise any changes.

Examine your breasts both standing and lying down. Stand in front of the mirror, lift your arms to the side, and check that the skin of the breast does not pull in.

Relax your arms on your tummy and use your left hand to check your right breast with the flat of the hand. Do not squeeze the breast or lift your arm above your head to feel the glands (lymph nodes). If your arm is bent, you can feel the glands beautifully.

Any pain, any nipple discharge, any mass, any “I am not sure” – see a doctor or clinic that has an interest in breast care.

Do not be afraid to question your doctors. Go for second opinions, and do not be pressured into unnecessary surgery to find out what something is. An ultrasound at a reputable unit for a young woman, and a mammogram and ultrasound if you’re over 40, is the way to start.

— Dr Carol Ann Benn

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