New and different ways of treating cancer

New and different ways of treating cancer

What determines how a cancer is treated? Are there certain rules, or do doctors just decide who gets what?

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. And how lucky some women are not to have to take Tamoxifen.

This article has been a long time in coming for me to write. As I sit in my anxious neurotic obsessive compulsive state (personality) on yet another flight back from an extremely productive congress addressing amongst other topics the importance of a ‘patient’s’ or anyone’s quality of life, I realise that my ADD type personality ensures this would be the time to write it.

So what determines how a cancer is treated? Are there certain rules, or do doctors just decide who gets what? Or do patients decide? In the old days, last century (that was not so long ago… only 15 to 20 years ago), the assumption was the bigger the cancer, the worse the prognosis. The bigger cancers got mastectomies, bigger cancers got chemotherapy, cancers over 5cm started with chemotherapy, bigger cancers got radiation.

The last ten years has brought an important fact to our attention: It is not about size, but rather personality.

Tumour characteristics determine some treatment rules

Do tumours have personalities? Sure. Does this determine how they behave and how we should treat them? Absolutely.

So if this was a Disney production, we could look at some of the baddies and translate them to the different type of breast cancers, I might mix my metaphors or my Disney and Pixar analogies, so I will stick to the analogy of clothes.

The characteristics or clothes that define a cancer are the following:

The grade: A pathology report will commonly say grade one to three, with grade one being slow growing and grade 3 fast growing. Relative to most cancers, breast cancers are slow growing, so when we say fast growing this is not little shop of horrors. There is always time to take with the decisions around what treatments to start with.

The division rate: This is called the Ki, and is a percentage, and gives an idea to the treating team how fast the cancer is growing (again this is not growing out of control daily). The analogies I use for the Ki are the shoes the cancer is wearing. Nifty little Christian Louboutin with the red sole or Jimmy Choos  are nice to look at but must be hell to walk fast in (ki,15% slow growing) ……you can then get a pair of sleek running shoes some for a fast marathon, and others with spikes for a sprint (extremely high Ki 70 to 80 % ). The very high Ki tumours are often but not always triple negative.

The glue: E cadherin is the name we give to a substance that ‘holds’ the cancer cells together. Duct carcinomas have Ecadherin and Lobular carcinomas have no e cadherin (think underwear. It holds us all together)

The receptors

Three important receptors that you should know about are the estrogen receptor (ER); the progesterone receptor (PR) and the Her 2 receptor.

We usually lump the ER and PR together, and they range from highly sensitive (above 66%) moderately (33-66%), and less than 10%, considered almost negative. 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.

If you are experiencing side effects that are making the treatment unbearable, please discuss this with your treatment team, as there are always solutions, ways to decrease the side effects, or other medicines available.

I often wish women would understand that taking their endocrine treatment is like taking an antihypertensive if you have high blood pressure. (If you don’t take your blood pressure medicines you can have a stroke or a heart attack).

Endocrine therapy is the oral contraceptive pill preventing cancer sperms from planting babies. It is 97% effective not a 100%. You can use the rhythm method, and not fall pregnant (not take your Tam) but the chances are higher that you will get a cancer recurrence.

The Her 2 receptor is a very important receptor and it is critically important that the test for this receptor is carried out on core biopsy, and if negative again on the final tumour specimen, if the scores are two or three, a test called the SISH or FISH (path lesson for another article) is carried out. Most but all (very tiny cancers <5mm) will require a drug Herceptin if the cancer is Her 2 positive (Herceptin is always given with chemotherapy as a general rule). Remember all patients diagnosed with breast cancer should be discussed in a multi-disciplinary team with many independent specialists.

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

Commonly today you may hear your doctor speaking about the type of cancer you have:

Triple negative: This means a cancer that is not hormone sensitive (ER neg, PR neg) and Her 2 neu neg. 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.

Most of them, except the very small and the very sleepy (low Ki), will probably need chemotherapy.

Her 2 positive; these tumours may be either ER and PR positive or negative but have a positive (rated as a 3plus, or FISH or SISH positive).

The below terms are all for Her 2 neg cancers:

Luminal B: A term that means a cancer is ER and PR positive (Her 2 neg), and has high Ki (over 15%). Most cancers can fit into this general category.

Luminal A: These cancers are lazy (low Ki <15%) and are all ER PR positive.

Other terms you may hear

Pagets Disease: This is a cancer that starts by spilling onto the nipple (not the areolar brown skin around the nipple). Some may be sleeping; others may have a hidden component in the breast (either sleeping or awake).

Inflammatory cancer: This presents as a red hot inflamed breast, and can be a difficult cancer to diagnose.

DCIS (duct carcinoma in situ): This is a cancer that has not woken up, like a car in idle it has not started moving. The analogy I give is of bulbs that you plant in the garden. You can plant them with all the condition to grow, eight grow and two do not.

If you put them in a dark garage cupboard for next season, eight don’t grow and two do. The problem is we can’t predict when it will grow, and what it will develop into – a Seymour (man eating plant from Little Shop of Horrors) or a local strangulating weed.

How long has the cancer been there for? Does size determine this?

A big luminal A tumour, may have been sitting in the breast for a long time without spreading, yet a small triple negative or Her 2 positive may have. So if it is not the size, but personality, then how do we determine the behavior? By checking the spread.

Cancer in the breast does not kill, cancer that has spread does. For this reason oncology (medicines that treat cancer) should always reign supreme. So how do we determine spread?

Radiology is a good way. Local radiology involves a mammogram and ultrasound. The reason for the ultrasound is also to look at the regional lymph nodes, those in the axilla (armpit) or supraclavicular area (neck). A good radiologist has a 95% plus sensitivity in assessing whether lymph nodes look involved or not. Radiology can also assess the rest of the body by means of different scans that again will be discussed in your MDT.

Our bodies are extremely clever and do not want a cancer growing, so they set up a security system. If you have tonsillitis, a gland can go up in your neck. If you have a breast cancer, a gland can be switched on in your axilla. This nominated first line security guard is called the sentinel lymph node (we have many lymph nodes in our axilla, at least over 30).

With certain types of cancers, or cancers over a certain size, I often check the sentinel lymph node as a small seven minute stand alone procedure if the radiologist has told me the glands look clear on sonar. The reason for doing this is it gives me critical information about the behavior of the cancer (its personality).

The old thoughts were if the cancer is small and the ultrasound is clear, the cancer probably has not spread and a doctor should start with surgery. I don’t like ‘probably’ when it comes to cancer. Some cancers have an ugly nature and even if tiny want to spread, so by checking the sentinel the doctor can be equipped with useful information. If this tiny cancer has spread to the sentinel gland, it is often better to start with chemotherapy, because as said before, cancer in the breast does not kill, it is the cancer that has moved elsewhere that has that potential. So if you know it is trying to spread, kill it, ‘doom it’ before taking it out.

Big cancers that are slow growing may have been sitting in the breast for a long period of time, particularly if they are hard to see. Lobular cancers are hard to see, and can sit in the breast for many years. So again, checking the sentinel on a big cancer and finding out that it has or had not spread gives useful information about treatment plans.

Oncology

I have specifically placed oncology above surgery, because I feel it is the umbrella under which all cancer treatment should fall. I have been accused in the past of calling myself an oncologist…I am not and this is usually as a result of some journalist that has inaccurately put that title next to my name. I love oncology and feel that it is a very clever, rewarding medicine.

I read extensively around breast oncology, and find the science behind the use of different drugs very interesting. I mention this so that people realise the time and effort that goes into the choice and the giving of oncology drugs, particularly chemotherapy. I am too blond and soft and love talking to my patients too much to do this challenging, often frustrating, and rewarding, but also at times sad, field. Oncologists are scientists and most are physicians as well. They are super-specialised in the giving of medicines, and can sometimes come across quite intimidating.

Oncology drugs are the antibiotics to kill cancers. Sometimes you have an antibiotic for a big, obvious infection like an abscess, sometimes you have an antibiotic but you can’t see an ugly bug. This is like oncology drugs.

Certain types of cancers will almost always require chemotherapy, some cancers require us to start with chemotherapy and melt the cancer away. These would be the big cancers that have spread to the glands, inflammatory cancers (present as a red orange peel looking breast), cancers that can’t be found in the breast and present with a big lymph node in the axilla, and smaller cancers in whom the sentinel lymph node is positive.

After surgery, small cancers that have not spread to the axilla, are discussed in the MDM. Certain cancers based on their personality usually get chemotherapy (mentioned above), and some luminal A and B cancers are often referred for genetic profiling to determine their genetic make up if it is difficult to read their personality from the path report as to their potential to spread.

The analogy is if your daughter is dating two men, and decides she wants your input as to which is Mr Right. So she brings young man home to meet you. He is gorgeous, well dressed, has a good job, drives a nice car, brings her flowers and mom chocolates and everyone goes THIS IS THE ONE.

The following night she brings home, Mr Biker dude who is dressed in leathers, has a few tattoos, and tells you he is a student of life, and everyone thinks OH NO.

Actually young man A is going to turn out to be a terrible husband, emotionally abusing her, a real psychopath. And Mr B will settle down, get a good job, and love her for ever. But the physical and the personality at the initial look fooled us all. That is why today we can do genetic profiling of tumours and look at their inner hidden workings, thus determining how they will behave.

In certain scenarios your treating team will recommend genetic profiling the tumour. This takes time and is done when we are not sure if there is value in giving chemotherapy. Again, as mentioned above, your oncologist will also suggest if you need endocrine therapy (all cancers that are ER; PR positive) must get these drugs and he/she will decide for what duration.

Should your cancer be Her 2 positive, you will probably receive a year of Herceptin (depending on your medical aid).

Radiation

I have put radiation before surgery, as radiation is always the poor cousin and offered last, after chemotherapy and surgery.

It is, however, critically important to know before starting treatment whether radiation is needed or not. Again, this highlights the discussion needed of every patient in the MDM. I have seen time and time again, the same mistake made by experienced oncologists, where patients are started on chemotherapy before surgery and documentation of the need for radiation is not clear at the start.

The poor women then goes through her chemotherapy, has an excellent response as is the usual scenario, and then no one knows whether she needs radiation or not.

Here are the radiation rules to be determined before treatment starts:

  • All cancers bigger than 5cm get radiation
  • All women who chose to have breast saving surgery get radiation
  • Any cancer that is in three or more lymph nodes or cancer outside the lymph nodes, extranodal spread
  • For discussion in the MDM
    • Cancer in one to three lymph nodes
    • Close margins from cancer in the surgical specimen
    • Sleeping cancer (DCIS)

Surgery

Surgery is for blondes, there are only two rules:

Rule 1: Take the cancer out with a clear margin (usually each unit decides on what that margin is, there is no consensus). Close margins are however associated with a higher rate of local recurrence, the cancer coming back close to where it was excised.

Rule 2: Check the draining lymph node basin. This is done by a sentinel lymph node biopsy or an axillary sampling.

Breast saving surgery must go hand-in-hand with radiation.

So if there are only two rules how come so many women have different procedures?

Well, firstly there are tumour personality factors.

Tumour: How easy is it to see it in the breast, how many areas of the breast are involved (muticentric: throughout the breast; lobular: no glue, difficult to see), how big is the tumour?

Breast factors: How dense is the breast tissue, could the cancer be seen easily, how big is the breast. So breast to tumour size ratio is important.

Patient factors: How anxious is the patient, does the patient have issues around radiation, how does the woman feel about future mammograms, does she have prostheses in, does she have a family history?

Doctor factors: What procedures is the doctor capable of doing, does the doctor work with reconstructive surgeons, is she or he trained in reconstructive procedures, have you spoken to patients who have been treated there before.

Patient characteristics determine treatment choices

At the end of the day, the above guidelines tell the patient who needs what treatment when. Patients’ individual choices also need to play a role. Each women and her relationship with her breasts is as different as each tumour differs from another. Respect, care and time are my advice. Don’t be pulled into ‘but Jane did, or so and so said’. It your body, your temple and you need to go through the processes slowly and carefully. Remember: once in the bucket, we can’t take it back. Each person walks an individual life pathway.

Doctor characteristics should just ensure safety guidelines

Although there are recipes, a good chef adds and subtracts secret ingredients, so as to ensure a unique dish. Experience, loving care, ambiance and company makes the meal special. So the team of the nurse navigator (thanks Julie), caring doctors, nursing staff, allied staff, family and friends are all contributing factors to decisions patients make.

I hope the above ingredients make your own special dish a successful gastronomic experience, Salute!