Triple-negative breast cancer

Professor Carol-Ann Benn reveals more about triple-negative breast cancer: the one you want to know about but may not want to know personally. The breast cancer everyone has Googled.

In the last issue, we discussed the lazy and slow lobular breast cancer. So, I thought I would dive into the deep end this issue and discuss the ‘dark side of the Force’ – triple-negative breast cancer. The upside is Darth Vader was conquered and beaten (and not all bad).

Let’s recap 

It’s no longer about size (stage). It’s not about age but rather about personality. 

A triple-negative breast cancer gets its name as it has no receptors for oestrogen or progesterone, or HER2 (three common receptors). Hence the name. 

This is not, however, one cozy nuclear family. In all families, you get upstream swimmers. In this family of cancer overachievers, you get those lazy triple-negative cancers that just don’t seem to belong in this ‘Addams Family’.

There is a group (salivary gland variant) that have low Ki-67 (<15%) and have no interest in getting up to mischief. Hence, they require little to no chemotherapy. This is a reminder that just because you have the same surname, doesn’t mean you behave the same way.

About 10 years ago, triple-negative breast cancer was the bad kid on the block. Twenty years ago, it was HER2 positive breast cancer (the next topic). And, in two issue’s time, I’ll reveal who the millennium troublemaker is – the one we need to psychoanalyse, and how to manage this potential troublemaker.

Spoiler alert

We diagnose a breast cancer with a core needle biopsy in a radiology suite (not with surgery). I stress this with triple-negative breast cancers as they can resemble fibroadenomas.

Triple-negative breast cancer is usually the cause in young women where a mass is considered a non-cancerous ‘fibroadenoma or cyst’, and the women are told not to do anything, or to find a friendly surgeon. Which is just so not the correct way to manage this psychopath! I can’t stress enough expert radiology and radiology-guided core biopsy of masses.

You want to study this terrorist before you lock it up

Who are they and what should be  on the wanted poster?

Triple-negative cancers account for 10-17% of all breast cancers. It’s considered significantly more aggressive than other molecular breast cancer subtypes. The majority are called grade 3 (this is not stage but a pathology interpretation of cells). Another pathology pseudonym is high-grade duct carcinoma of no specific type (read into this as it may also be travelling under the name of).

Bad characteristics (prone to violence) are their propensity to cause distant spread within a short time; possibility for chemo-resistance; lack of molecular targets for treatment (finding the terrorist footprint so we can chase it, or see it and kill it, is critical in finding cancers). They have a weak relationship between size and spread to lymph nodes; i.e. can be small and send cells to the lymph nodes (security system). They have a higher risk of coming back in the first three years. But as time goes by and once past five years, they have less   and less chance of reoccurring. 

Triple-negative breast cancers are a group of significantly different biological baddies. Yet, some are just significant wimps if you nuke them upfront. And if the kill-rate is 100%, they have less chance of coming back.

Steps to nab it

1. Place a marker into the cancer prior to starting chemo. The cancer can fade fast on treatment and you need to know where it was. Behaviourly, this tumour is a bit of a bully and with the right meds upfront, it can roll over and expose a very weak belly inside at speed. I’ve personally had those embarrassing multi-disciplinary meeting (MDM) moments where we thought we could put in a marker after one chemo and ‘poof’ the cancer is nowhere to be seen after one chemo.

2. Putting the baddie in interrogation allows us to study behavior quirks. These tumours can look bland clinically and radiologically (with not having receptors for hormones or HER2). They try to blend in. 

But on closer inspection, those twitches; that inability to sit still; that high Ki-67 (they just want to move), they actually do have receptors and traits that allow ‘clever detective’ pathologists and oncologists to type caste behavior traits. Resulting in permanent lock-up and lethal injection for good. There are actually six variants described on gene expression. 

Information, such as lymphocytic infiltration, Ki-67, and androgen receptor, allows the treating team to assess ‘best-kill strategies’ as well as knowing if the tumour has developed in a person who may be a BRCA-gene carrier.


The pathology team and MDM are like detectives when we work out the type of psychopath a triple-negative is, in order to formulate a treatment (kill) plan.

Almost all these cancers require some form of medical oncology treatment (chemo). Most specialist units today will recommend starting with chemotherapy.

If you’re diagnosed with triple-negative breast cancer, please do not rush into an operation until a full review is done by a MDM unit that can show you stats on their treatment outcomes.

In fact, I recently visited an excellent national health unit in Surrey and met a specialist with such similar thought processes. Yes, they also kill these tumours first, even if very small.

Fibroadenomas are the commonest type of lumps found in young women; 10% of breast cancers in women under 35 present resembling fibroadenomas.

So, if you’re a medical hitman or a super-armed Forces dudette, you want to ensure you’ve rounded and sorted your entire terrorist motherload before just catching some and scrambling to see if all are caught. This includes stragglers and outliers (sleepers can be sent to the brain).

The concept of kill in most triple-negative cancers is to kill the tumour before removing it. So, although I have never met a single person who has signed up for a “I want to have a chemotherapy trial”, we need to understand again that oncology drugs are the antibiotics to kill cancer.

Why do we give intravenous chemotherapy and not a tablet?

I’m often asked about rather having   a tablet instead of a drip. Well, if you want effective treatment, you don’t want your access to be 200 soldiers, down a small entrance (oesophagus) with an acidic holding cell (stomach), before heading down extensive loops of bowel, trying to access the blood system while putting on those killer night goggles and looking for stray cells randomly. Much easier to shoot into the action is down the bloodstream river that ensures access to all potential hiding organ sites.

Your oncologist will advise types of chemo for triple-negative breast cancers. Please, again review an opinion before starting.


Personally, docetaxel, doxorubicin  and cyclophosphamide (TAC) (atTACk) with growth support (i.e. protect and stimulate the locals to boost the immune system) has excellent results in six cycles.

If there is a poor response, determined on ultrasound, second-line platinum-based therapy is amazing. There is excellent new data on: if you can’t give TAC; giving AC and with the T-arm, adding a platinum.

I, personally, think, although not backed by data, that triple-negative cancers laugh at weekly taxol.

Assessing response to this cancer is best done radiologically during chemotherapy. Most commonly with an ultrasound.

Technically, the breast cancer rule book says…that if it’s not in the glands (lymph nodes) prior to starting chemo; and not after chemo at definitive surgery; and if you do a mastectomy, you don’t need radiation treatment. That is a whole lot of ifs!

We prefer to radiate in triple-negative breast cancers in our unit.

So, encourage an accurate node assessment prior to staring chemo;  and encourage breast-saving surgery. Thus, ensuring radiation.

Remember, surgery is for blondes. Only one rule: take out the cancer   with a clear rim/margin. T&Cs apply in different units. It’s not better to take off a breast. Breast cancer does not spread from one breast to another FYI. So, taking off both doesn’t   avoid chemotherapy…ever!

Elderly unfit patients

What about the elderly unfit patient in whom primary chemotherapy is not an option? Those that are operated on first, due to concerns regarding fitness for managing primary chemotherapy.

Classic cyclophosphamide, methotrexate and 5-fluorouracil (CMF) works in a subset of triple-negative cancers, in the adjuvant (post surgery setting). My concern here is, this is still treating blind as you can’t see the effective kill-rate on this tumour with ultrasound imaging during treatment. CMF doesn’t work well in these cancers in the neo-adjuvant (chemo before surgery) setting.

What about that monster in the room?

The tumour that doesn’t shrink  with chemo. Usually, the panic is: it isn’t dying so operate, remove it, operate. Panic! Actually, second-line chemotherapy is a better option. Remember, killing the alien has not prevented it from having laid eggs.

Obviously, at some stage, we just say ‘Just do it’…we are having no luck with medicine and we do operate. These moments are preceded by self-doubt and robust, argumentative MDM discussions. 

We must remember that this is just a panicked “alien moment”- that big ‘hit the nuclear button’ moment. One day, (and we’re getting there, this is for sure) we will have special targets and immunotherapies, better than Sigourney-Weaver-alien-killers. I have the pleasure of seeing this in the MDM I am part of – a specialist oncology unit with super success and kick-ass trials and publications on this. Well done Prof Bernardo Rapoport.

After MDM discussion 

Of all cancers, triple-negative breast cancer particularly should be discussed in a MDM. Leave it, give chemotherapy; kill it, remove the skeleton, and if you achieve a 100% kill-rate, the chance of it coming back gets less and less over the years.

And, yes, there are maintenance therapies in triple-negative breast cancers. A wonderful trial has shown that patients who don’t have a pathological complete response (PCR), which is a complete kill-rate with these cancers found at surgery, should get an oral chemotherapy after surgery. The outcomes are excellent.

So, as always…

Writing on a plane (a reminder of  the fragility of life) makes me just want to end by saying: Yes, triple-negative breast cancer is a baddie. But, don’t rush into surgery. Ensure good MDM review. Our clever oncologists are revealing this    tumour to be a soft-bellied, killable psychopath. Google that Con Air scene, where that awful killer hands the little girl her doll back (life) and walks away.

Yes, thank you clever oncologists. This tumour is the one I think you finally have a handle on.

Prof Carol-Ann Benn heads up an internationally accredited, multi-disciplinary breast cancer centre at Netcare Milpark Hospital. She lectures at Wits University and, in 2002, established the Breast Health Foundation.Prof Carol-Ann Benn heads up an internationally accredited, multi-disciplinary breast cancer centre at Netcare Milpark Hospital. She lectures at Wits University and, in 2002, established the Breast Health Foundation.

MEET OUR EXPERT – Prof Carol-Ann Benn

Prof Carol-Ann Benn heads up breast cancer centres at Helen Joseph Hospital and Netcare Milpark Hospital. She lectures at Wits University and, in 2002, established Breast Health Foundation.