We learn more about Prof Carol-Ann Benn’s analogy of luminal A breast cancers: lazy Cartoon Network baddies.
When thinking of luminal A breast cancers, think Cartoon Network baddies. Not scary at all but you must deal with them, or you will land up playing rerun after rerun.
Luminal A breast cancers are the most important reason to screen. This is a lazy cancer. If you detect it really early, the survival is excellent.
Let’s define this Cartoon Network baddie
Extremely hormone-sensitive. This doesn’t mean that the cancer is caused by hormones but rather the cells have receptors to oestrogen and progesterone (these are ER and PR positive) and the division rate is low (Ki-67 <15%). Think high heel shoes with less ability to run.
But like all cartoon baddies, they can certainly misbehave and have many different personalities. Think Tom and Jerry, Dick Dastardly and Pink Panther.They are difficult to detect as baddies.
Detecting this baddie may be challenging
Some luminal A breast cancers can be hard to see on mammograms and ultrasounds. Due to them being inherently lazy predators, they can be missed.
On mammograms, some breasts are dense (breast density is often greater in women on hormone replacement therapy and on the oral contraceptive pill in their 40s). The problem with dense breasts is it makes finding the Pink Panthers challenging.
Remember, the bush analogy: dense bush (jungle) makes it hard to see the lazy predators.
Some, like tubular cancers, may mimic non-predators and may resemble fibroadenomas to the untrained eye and can sit around for a long time and be mistaken for a non-cancer.
Tubular cancers are the laziest of all the breast cancers. I have spoken about lazy lobular cancers (a type of luminal A cancer that resembles ants walking along a wall; this making it extremely hard to see).
So, remember because luminal A cancers are lazy, they may be hard to see. Like looking for the shy five in the bush. MRI is of value in detecting these cancers (flying in a helicopter and looking from above).
Another problem with these cancers, is people feel their breasts and think this doesn’t feel much different to the last time I checked. And, the longer you leave it, the more it sticks and the harder these cancers are to extricate. So, if it doesn’t feel right no matter what the mammogram says, ask for another ultrasound and a core needle biopsy (not an operation).
Once the little devil is caught; now what?
The rule around most luminal A breast cancers is that they almost never need chemotherapy. Why almost never? Because if left for long enough, then you need some serious manoeuvres to remove them. As one of my favourite oncologist always says, “Removing advanced luminal A breast cancers is like trying to get chewing gum out your hair…takes a lot of work…and you may not get it all out.”
As with all breast cancers, an understanding of the size of the cancer in relation to the breast size; the position of the cancer in the breast; and whether the ultrasound has determined if there is cancer in the lymph nodes is needed.
With advanced luminal A cancers that are big and in the lymph nodes, it’s important to determine if there is any cancer elsewhere. This is done by asking if there are any symptoms, such as bone pain particularly, or shortness of breath, or any other concerning symptoms.
We divide luminal A into: early stage (surgically resectable); advanced stage (with spread elsewhere) and locally advanced (big and not easily resectable with no spread elsewhere).
Remember, all breast cancers should be discussed in a multi-disciplinary meeting (MDM) with specialists from all different cancer disciplines. The pathology and films should be visualised for all; and the feedback should be by an independent navigator system.
The mainstay of treatment for many of these tumours is surgery: cutting the gum out the hair. The type of surgery will depend on the size of the tumour to breast ratio.
Remember the following rules:
- Breast-conserving surgery has equivalent survival to mastectomy.
- Cancer doesn’t spread from one breast to another.
- If there is cancer in the glands/lymph nodes then radiation is needed.
- Taking off both breasts doesn’t prevent cancer from spreading, or one not needing oncology treatment.
- Some very lazy luminal A cancers can be treated with hormonal treatment prior to surgery; or in a subset of frail patients – only with this group of medications.
- It’s important to mark the cancer with either a titanium marker or a magseed (magnetic marker). This is the X marks the spot for knowing where the cancer is.
Oncology treatment for Luminal A breast cancers
The mainstay of medical oncology treatment is a group of medications, called endocrine therapy.
One of the breakthroughs in breast cancer treatment was the discovery of drugs targeting the oestrogen-signalling pathways in the early 70s. The one most often googled is tamoxifen.
Tamoxifen is not a hormone blocker but rather a selective-oestrogen receptor modulator (SERM). This means that it has both positive and negative oestrogen effects on some organs (heart, bones, uterus, and veins). In fact, it’s the oestrogen effects that people are most concerned about (clots in the veins, and uterine cancer – the risk is very low).
Tamoxifen, initially named ICI 46 474, was the first targeted cancer therapy against this pathway approved for the treatment of breast cancer.
The endocrine treatment for luminal A breast cancers used to be that young pre-menopausal breast cancers had tamoxifen; and postmenopausal had either tamoxifen or aromatase inhibitors (AI). In fact, we even used to say that young women need chemotherapy. We now know that this is not true.
The rule now is that we usually give either tamoxifen or AI in young women (any one not yet in menopause) if we have switched their ovaries off. This is done with a group of medications, called gonadotropin-releasing hormone (GnRH). This is a chemical way of temporarily switching off the ovaries. Many moons ago in the 50s, people would remove the ovaries to treat breast cancer. In the 1890s, Sir George Beatson showed that most breast cancers in young women responded to taking out both ovaries. The value of a chemical menopause is that the injections can be stopped as some young women may desire a pregnancy post breast cancer diagnosis.
GnRH analogues, such as Buserelin and Zoladex, have been found to have similar anti-tumour and hormonal effects comparable to surgical ovariectomy. But, please don’t rush into surgery unless you have spoken to your multi-disciplinary team. Surgery has complications and can’t be reversed.
#Aromatase inhibitors (AI)
AI catalyses the final and rate-limiting step in the making of oestrogen. Inhibitors of this enzyme act as effective targeted therapy for breast cancer. Three main AIs are used: Arimidex, Femara and Aromasin, and a variety of generics are now available.
This alternative approach without targeting ER directly was hypothesized to be more effective with fewer side effects. Harry and Angela Brodie were initially working on the biochemistry of aromatase and were developing the inhibitors of aromatase as potential contraceptive agents but also as improved treatment for breast cancer. The first series of these compounds were created in 1973.
Treating slow-growing cancers is about long-term endocrine treatment.
A minimum of five years; most likely seven to 10 years, and maybe even one day we will need life-long. Not dissimilar to treating blood pressure, cholesterol, epilepsy or diabetes.
Compliance is critical
The importance of compliance is critical. Please see your treating team if you have side effects rather than not taking treatment. As said before, catching this Cartoon Network baddie once it has escaped, is difficult and involves many reruns of different treatments and usually a life-time of cancer treatment.
Advanced luminal A breast cancer
When these baddies present as big and advanced in the breast, they can be tricky to manage and require a complex multi-disciplinary approach.
We sometimes need to use chemotherapy agents that are better at managing slow-growing cancers (weekly Taxol). The aim is to melt the cancer to a size that makes surgery effective, so that the cancer can be removed clearly; and then look at other treatment afterwards.
The problem with these cancers is that they are like fungi. They can just keep on coming back. There are a variety of hormonal drugs that can be used. For example, in advanced luminal A cancers that have spread, treatment with endocrine therapy can be used and not just treatments, such as chemotherapy. There is an injection, called Faslodex (fulvestrant). It’s an oestrogen receptor antagonist used to treat hormone-related breast cancer.
Other clever drugs are: CDK4/6 inhibitor – either palbociclib or ribociclib; mTOR inhibitor and everolimus.
Remember, there are often trials and new developments in the field of metastatic (spread) breast cancer and there are many breakthroughs happening all the time. So, ask your oncologist, or ask for a discussion in the MDM.
Understanding oestrogen in terms of cancer
Oestrogen is known to be important in the growth of breast cancers in both pre- and post-menopausal women (it’s a fertiliser).
Although oestrogen is no longer made in the ovaries after menopause, peripheral tissues (particularly fat) produces sufficient concentrations to stimulate tumour growth. So, get fit; train and watch your weight. Maintain a BMI under 25.
New and exciting research
T&Cs apply and most importantly a discussion in the MDM…So, although the rules are that all women who have breast-saving surgery need radiation; a subset of elderly patients with luminal A may not.
A further subset of node (gland) negative luminal A may fit criteria for intraoperative radiation (given after tumour is removed during surgery). Some may only require a shorter course of radiation.
Watch this space as cryoablation treatment for these cancers is soon to hit our shores (see the FROST trial). This means no surgery for some (T&Cs).
But, don’t be fooled. This Cartoon Network baddie can get up to mischief if not treated. But, what a pleasure to say that it so can be super sorted!
This means switching channels and forgetting about it. That’s all folks.
MEET OUR EXPERT – Prof Carol-Ann Benn
Prof Carol-Ann Benn heads up internationally accredited, multi-disciplinary breast cancer centres at Helen Joseph Hospital and Netcare Milpark Hospital.She lectures at Wits University and, in 2002, established the Breast Health Foundation.