De-escalation of oncology care

Professor Carol-Ann Benn examines the timelines of oncology care and how changes in treatment have resulted in our modern-day approach.

---

You can listen to this article below, or by using your favourite podcast player at pod.link/buddiesforlife

Historically breast cancer was treated primarily by surgeons; then once it was understood that advanced cancers didn’t do well with surgery, oncologists (physicians) got involved. And slowly over the many ages of cancer evolution, changes occurred that resulted in improved patient survival and longevity.

Prehistoric oncology era

The first prehistoric age was that of the radical mastectomy; with not just the breast being removed but all the underlying muscles and all the lymph nodes possible (21+). This morphed into the concept of treating breast cancer by stage. This very formal era consisted of dividing breast cancer into: T (tumour size) stage; N (nodal involvement) stage; and M (metastatic) stage. Whilst today we also document this, many staging versions of the TNM classification have fine-tuned the role that this staging plays in treatment.

During this age, breast cancers were loosely divided into early stage and late stage. With early stage getting surgery, usually mastectomy, and late stage getting chemotherapy. Both treatment arms were fairly recipe-based in terms of treatment options offered.

Further understanding that breast cancers had a hormonal drive, resulted in dividing patients into those who were premenopausal and post-menopausal as an aid to treatment decisions. Resulting in the addition of; if you were young, you would get chemotherapy as well, and if you were older, you would get a hormonal blocker.

Finally, as we headed out of the Jurassic era, the pathologists realised that by studying the cancer cell in more detail, breast cancer could be divided into four biological (behavioural) types and so we moved into the modern era of treating breast cancer, based on the biology of the cell. 

Current modern era

The amazing era of modern breast cancer management today revolves around two important concepts: de-escalation of treatment in all arms of care (oncology, surgery and radiation) and personalised cancer care.

Let’s start by looking at how de-escalation of care has happened, and a bit like in evolution, certain events coincide and that often fast-tracks change.

The Renaissance era

This era was about understanding beauty and preserving breasts.

With regards to surgery, the radical mastectomy was challenged by the women’s movement in the late 60s, with the question being asked: why were men making decisions to take off a part of their bodies that was integral to their very sense of femininity? Bernard Fisher (USA) and Umberto Veronesi (Italy) pioneered these changes.

Surgeries involved removing initially a quadrant of the breast (as it was thought the safest) followed by some rather brutal radiation, and were only offered in women whose cancers were early stage and small. No cancer bigger than 5cm or any cancer that was in the lymph nodes or involved the skin were offered breast-saving surgery. It was considered crucial to do a full axillary lymph node dissection which involved removing up to 21+ lymph nodes. Over the next 20 years, the number of nodes that constituted an axillary dissection decreased from 21 to 15 to 12 to now seven.

The aesthetics of these surgeries weren’t great and over the next 10 years plastic surgeons would offer options of regional muscle flaps and other techniques to fill the defect. Werner Audretsch developed techniques to rotate breast tissue and so the field of oncoplastic surgery was born. As we fine-tuned the amount of clear margin we could leave around the cancer, the ability to aesthetically reconstruct the breast became easier with pioneers, such as Krishna Clough, setting up oncoplastic difficulty levels for teaching breast surgeons and reconstructive surgeons, based on breast and tumour size and position.

2000 to 2010 era

What helped during the 2000 to 2010 era was the use of neoadjuvant chemotherapy (before surgery) and trials with HER2 targets that showed that one could decrease the size of the primary tumour and this would then help save the breast. Naturally there were T&Cs.

Tracking forward into 2010 plus, we started to see that actually margins with regards to breast conservation were less important and that although close margins may impact on the local change of the cancer coming back, this didn’t affect overall survival.

As the studies started to show that breast conservation surgery and radiation had an equal survival to a mastectomy (previous gold standard) and with improved pre-surgery chemo, the concept of a size of cancer being a reason to avoid a breast-saving surgery fell away.

More techniques were fine-tuned so that today we can take out cancers even if there is more than one in the breast and in many quadrants of the breast. Furthermore, there are even studies now to see which patients may avoid surgery altogether, particularly in women who have primary chemotherapy. The future lies in smart biopsy guns to determine if there are any residual cancer cells and in freezing certain tumours by means of cryotherapy as we move into the sci-fi realm of surgery avoidance. The data started to emerge that not only is the-less-is-more-approach good for patients from a psychological point of view, but actually the survival data in women undergoing breast-saving surgery with radiation may be better than in those undergoing a mastectomy.

The sentinel lymph node era

Many studies are underway to work out which patients may avoid surgery post primary oncology. As the radiological ability to assess cancers improved and the use of ultrasound assisted in determining if there was any cancer in the glands with early stage cancers, the adoption of a new and novel way to assess the drainage lymph node basin began.

The birth of the sentinel lymph node era (security guard) or first lymph node that the cancer drained to in early stage cancers resulted in us starting to realise that maybe it wasn’t necessary to take out all the lymph nodes in the bid to prevent cancers from spreading, but rather realising that the first gland that the cancer drained too signified a prognostic significance. So, the rules of the game changed yet again, and we realised that we only needed to do an axillary dissection in patients who were confirmed node positive.

As the studies highlighted more benefits for only removing the sentinel lymph node and sometimes two surrounding lymph nodes, the sentinel lymph node biopsy became the gold standard for assessing the lymph nodes in early stage (node negative) breast cancer.

The boundaries as to what to do if the sentinel was positive and was there a need to go back and do more surgery were trialled and it was shown that if radiation was given to the axillary basin, then it wasn’t necessary to re-operate and complete an axillary dissection.

Renaissance era of the axilla

We started to use smart tracers to find the sentinel (Magtrace) and slowly as we were able to kill cancer cells with primary oncology treatment, the concept of not doing an axillary dissection in confirmed node positive patients, particularly post primary chemotherapy, has evolved. By localising the positive gland pre-chemo and placing

a clip (magnetic one) which you could detect later, one could give oncology treatment followed by detecting the localised gland and sampling only a few, and voilà no more axillary dissections. Well, could we now avoid axillary surgery completely? Let’s be honest, even with the decreased lymphoedema rate with not doing an axillary dissection, patients still complain about discomfort with a sentinel lymph node dissection. The future is when we won’t need to even do a sentinel in patients who are older and in patients with extremely lazy tumours that are small (SOUND trial released excellent data) and who knows from here. So, as surgery has moved from looking a little bit like a T-rex took a bite out of some Florenzi statue to actually look like how small David’s bits are (sign of class and apparently not to distract from the beauty).

Oncology drug advancement

Remember when I spoke about inflammatory cancers and surgeons in their god-like state declaring this can’t be treated, see your nerdy physicians (1952). Then the nerdy physicians with the bombs-in-the-hole-approach managed for patients to survive. Well, it all moved forward with pandemonium and trying to take cover (bombs-away-approach) of the first World War.

Whilst the smell of sulphur was still strong in the air, the oncologist actually stepped back and looked: they weren’t the most attractive bunch (who wants to go for chemo) so as they were working out doses not to kill people but rather to kill the cancer and cope with the maiming of the host. The oncology world was always ready for a terrorist insult, had a bit of a bombs-in-the-hole-approach. Siren and drop the bomb. At one stage, any cancer bigger that 10mm was offered chemotherapy. Sadly, although this worked, the casualties of war were evidenced in the patients’ long-term side effects.

As the pathologists worked to understand that not all cancers were the same, the concept of understanding the genetics of cancer cells by means of genetic profiling started. This allowed them to realise whether chemotherapy was actually needed, initially for patients with cancers that weren’t in the glands and now for those that had cancer in the glands.

Evolution of clever drugs

At the same time, evolution of clever drugs, targets and immunotherapies resulted in the use of less aggressive oncology regimens and more options given to patients. The COVID pandemic did a lot to fast-forwarding personalising cancer treatment based on the patient (considering medical and social circumstances).

The future now looks at understanding the relationship with the micro-environment around the tumour and the tumour’s ability to react and communicate with this environment. Cell-immune based therapy. Think like in the pandemic; the same virus had hugely different effects in different people. Yes, we know that if you were obese, diabetic and had underlying medical problems this didn’t help; but we also saw that some healthy adults got very ill as their immune system overwhelmed them. These concepts of the cancer cell and the micro-environment are being studied by many. The future is in liquid biopsies. Finding tumour cells very early on and manipulating the micro-environment around the tumour that has a love/hate relationship with the terrorist cell. Then for the pathologist to gene sequence the cancer so that the drugs used are personalised.

Era of less is more in radiation

Always the wall flower at the dance, the last member of the oncology treatment arm. Radiation took a while to come into its own. Initially, the significant local side effects resulted in the concept of radiation avoidance. So, radiation was only used for advanced cancers, and in women undergoing breast-conserving surgery. In fact, at one stage the surgical push was to have a bilateral mastectomy with implants so as to avoid radiation and have Barbie boobs that look the same. As we realised that silicone implants aren’t inert and actually the local environment response reaction has minor and major effects.

In the early 2000s, we realised that if you have more than four glands positive in the axilla, radiation improves outcome. Then in 2011, we realised that if any glands were involved with cancer, radiation improved outcome. This was then facilitated by what to do if the sentinel was positive (at this stage we went back and completed an axillary dissection). The studies, z11 and AMAROS, showed that radiation outcomes with giving radiation and not completing the dissection were better due to less complications of lymphoedema and less cancer recurrence. So, the wall flower was finally on the dance floor.

The next step was to fine-tune the radiation and see if less radiation could be used. So, we have now fast-tracked to the era of less is more in radiation with: if you have an early stage breast cancer, you may be able to have as little as five sessions of radiation; some women may even avoid radiation.

What about endocrine therapy?

Many women complain and google all the side effects. There are some genetic profiles available for low-grade tumours to assess the systemic value of taking endocrine treatment. A big T&C here is that endocrine therapy actually assists in preventing new cancers. So, over time treatment has de-escalated and become more patient-centred.

Who knows what the future holds for oncology care? But to ensure you’re not advised to take off both breasts (it sounds like you’re being presented with a recipe), ask for a review or a second opinion and ensure that the multi-disciplinary review isn’t doctors agreeing with one another but rather discussing the new and novel.