What the Walrus said.

The media are at it again, beating the data-drums for scraps of hope. It’s not that we don’t all long for reassurance and want to believe in the steady march of Science; it’s more that we can’t shake the suspicion that if we wish hard enough, stuff happens. For some reason I am reminded of the legends of the knightly quests for the Holy Grail where, to mix metaphors, ‘Lord Ronald said nothing; he flung himself from the room, flung himself upon his horse and rode madly off in all directions’ as Stephen Leacock would have it.

A bit of a stretch, perhaps, but a news report that I happened upon, brought it to mind: http://www.bbc.com/news/health-35111443 It was commenting on a large study on screening for ovarian cancer reported in the Lancet that looked at the value of a well-known cancer blood test (Ca125) coupled with ultrasound, and contrasted it with the value of ultrasound alone, or no screening at all. They were trying to ‘establish the effect of early detection on ovarian cancer mortality.’ In all, over 200,000 women were studied over a period of four years. And the results? ‘Their initial statistical analysis of the data showed no benefit to screening. But there was a benefit when they removed the data from any women who may have already started to develop ovarian tumours.’ [Bold letters and italics mine] Umm, I thought the whole idea was to find asymptomatic people who might have tumours…  And, as the news report does acknowledge, ‘…the interpretation is a bit messy and the researchers admit it is “controversial”.’ And yet, the article’s title screams: ‘Ovarian Cancer: Screening may cut deaths by a fifth. Buried in the second to last paragraph, however, is the more important point from Dr. Fiona Reddington, from Cancer Research UK: “While this is an important step in ovarian cancer research, we would not recommend a national screening programme at this point.”

I suppose my somewhat cynical point is that one has to read more than headlines to know the world, and that it is probably unwise to believe everything that is offered by the Media anyway… Then, for some reason, I remembered how I had managed to misread Germaine and her wish to be screened.

I like to see people smiling in the waiting room –it makes me want to choose them as the next patient and forget the scowlers or the eye-predators who attempt to capture me even before I make it past the front desk. Germaine imprisoned me with her eyes the moment I saw her –but more like in a flower than a jail. Her smile grew wider, the closer I approached, and almost exploded when I shook her hand to introduce myself.

But it faded slightly even after she realized she had in fact been chosen as the successor to my last patient, and had firmly ensconced herself in the hard wooden seat across from my desk.

The time has come, the walrus said…”. Those were the first words she uttered as soon as she sat down but when she saw the expression on my face, she managed to produce an embarrassed grin. “I’m an English Lit major…” she added, as if that were the definitive explication of the quote.

“The Walrus and the Carpenter -Lewis Carroll, right?” I said, surprised at how quick I’d got it.

I was rewarded with a twinkle from her eyes. “I have come to talk of many things,” she added, and promptly went on to explain. “I want you to check me for everything.” Her face glowed with expectation.

I tried to keep my eyes from rolling, but I’m not sure how successful I was. I then attempted to disguise my reaction further by scrolling through her records on the computer. I had seen her before, but not for a year or two. At that time, she had been referred for a pap smear and a discussion about becoming pregnant. She was now 26 so I assumed she was probably newly pregnant and was coming to me for her first prenatal visit. But the current referral letter said she was not pregnant and hinted at something else –something unspecified. I hate letters like that. I smiled anyway and looked up at her.

“My partner decided to be unfaithful, and said I need to be checked,” she said quite matter-of-factly as soon as she saw she had my attention.

Now we were on more familiar territory for me. I glanced at the screen. “Well, the pap smear your GP did a couple of months ago was normal…”

She looked as if she were about to roll her own eyes. “Well, of course…”

I politely ignored the unexpected reaction. “And you’re not having any symptoms?” Even if she weren’t I would still do the same tests, but it never hurts to ask.

“You mean like with gonorrhoea or syphilis…?” Her eyes narrowed slightly as she considered the ramifications.

I nodded. “Or chlamydia…”

She shook her head vehemently –almost violently, actually. “No, no. That’s not an issue.”

“Well, are you concerned about HIV, or…”
She threw her hands up in a theatrical denial of the very thought. Her mouth managed to roll up this time to complete the rejection. “Doctor!” she almost whined. “It’s not that kind of thing…!” But her sentence trailed off suddenly, leaving me to wonder if there was something she had been hiding from me. Something that she expected me to investigate without actually naming it.

“What would you like me to check then, Germaine?”

She looked down at her lap for a moment, the smile a mere ghost of its former self. She had pasted on another paler version by the time she looked up again. “Can I ask you a question first, doctor?”

“Of course you can…”

“Ahhh, I umm, read somewhere that ovulation drugs can give you cancer… ovarian cancer… Is that true?”

I had to think for a moment. There had been a spate of studies a few years before looking at the risk of ovarian cancer after the use of Clomid (clomiphene is a medication that tricks the pituitary gland into manufacturing FSH and LH which stimulate ovarian egg maturation and subsequent ovulation). The early and smaller studies suggested a slightly increased risk, but later studies either were unable to establish this, or had mixed results. “Well, those early studies were small and somewhat controversial, Germaine, and even with long term use, the risks were still very small…May I ask why you’re worried about this?”

A silent anguish seemed to drift across her face. “Well, what I read was that the longer you take the medication, especially if you don’t become pregnant, the greater the risk.”

“And did someone put you on it, Germaine?” I scanned through my old history but could find nothing to suggest a reason she would be infertile.

She nodded. “My GP did. We’d been trying for pregnancy for almost 6 months with no success.” She glanced at the ceiling for a moment and then out the window behind me. “And I mean the guy has good sperm –it worked before on another woman…”

I stared at her for a moment; I didn’t mean to, but my eyes just seemed to attach to her face. It was a rather odd way to talk about things. I decided to ignore it. “And how long were you on the treatment?”

She thought about it for a moment. “Well about 6 months, I think. But it didn’t work!” She took a deep breath and let it out slowly. “I told Jo -my partner- that I was worried about the risk of the Clomid… Then we both became worried, and that obviously led to the alternate route.”

“The alternate route?”

Germaine stared back at me with a puzzled expression on her face. “Yes,” she said after she’d thought about my reaction. “We both wanted a child and if I couldn’t be the one to carry it, then we’d have to make other arrangements –and it would have to be with someone else.”

Surrogate pregnancy?  I thought that was a little drastic after only 6 months or so of trying and I said so.

She looked surprised. “Oh it’s okay, she didn’t mind.” Then her eyes narrowed and a naughty expression suddenly laid siege to her face. “It was me… I was just a little surprised at the methodology, that’s all…”

By now I was hopelessly lost. Germaine seemed to find my puzzled expression funny and she started to laugh. Then her eyes twinkled again as the truth dawned on her. “I think you should look a little closer at the history you took when you first saw me.”

I pulled it up on the screen again and blushed. It’s funny how you can miss things when you’re searching for something else entirely.

“Even our eyes get caught in ruts, doctor,” she said when she saw my face. “It seems a shame, the walrus said, to play them such a trick…”

The poem again! But I finally understood; Jo had decided to have the baby.

“And my risk of cancer?” She was in a better mood now, and didn’t seem as worried.

The night is fine, the walrus said…” It didn’t really fit, I suppose, but the line had probably lain dormant in my head since university and I had to try it out.

She looked at me for a second and then giggled. “We’re really milking it, aren’t we?”

“You mean the butter’s spread too thick -as the walrus said?”

She nodded and then corrected me. “It was the carpenter…”

Breast and Ovarian Cancer Screening

I am sometimes troubled by the concept of risk. I mean how can we possibly decide whether or not a risk is acceptable? No matter the statistics, if the issue under consideration doesn’t happen, then the risk assumed was acceptable. So far, so good. But of course the converse is also true: no matter how low the risk, if it does occur, well…

Ours is a culture of prediction. Statistics. Guessing. I rationalize buying a lottery ticket by convincing myself that if I don’t buy it, I won’t win -no matter how low the odds, no matter how unreasonable it would be to assume that I would be the one in –what?- ten million who wins the jackpot. Or anything, for that matter…  And no matter that without a year of such profligate spending, I could treat myself to a sumptuous dinner at a good restaurant.

Of course, we all live in hope, and if the lottery ticket funds some worthwhile government project, then it is an almost enjoyable form of indirect taxation. Assimilable because it is freely chosen. Optional.

It is a different proposition entirely if the risk is one to which we do not wish to subscribe but have no choice: genetic defects in a developing pregnancy, cancers, diseases, to name but a few. It is likely to our advantage to interrogate these, if possible. Of course, the question then becomes who should undergo the screening. Only those at the highest risk –those with a family member with the condition, say- or everybody? Just in case.

Screening always seems to be bathed in a soft, warm glow. If you can test, then why not? Just pop in to your local lab and get that PSA; find out if your prostate is betraying you. Demand yearly mammograms as soon as you feel concerned. As soon as a friend or even a friend-once-removed has a cancer scare. And at any age, because you never know…

If only screening was that good; if only all negative tests were reliable –and, for that matter, didn’t have to be repeated at intervals to keep pace with the ravages of Time wreaking its not so subtle havoc on our aging bodies.

Screening for specific inherited genetic mutations for breast and ovarian cancers are the relatively new species of Wunderkind: BRCA1 and BRCA2. These are tumour suppressor genes broadly speaking; we all have them, and they are located on chromosomes 17 (BRCA1) and 13 (BRCA2). But if they contain defects -mutations- they may no longer function efficiently and so be unable to winnow out mistakes such as tumours from proliferating. The mutations are inherited in an autosomal dominant manner and women with these particular mutated genes have a lifetime breast cancer risk of 50-85%. .

So why not screen all women for these genes? Indeed, a recent study published in the Proceedings of the National Academy of Sciences (USA) suggested just that: http://www.pnas.org/content/111/39/14205.abstract

On first reading, it sounds like a reasonable approach. But I’m not so sure. First of all let’s put the whole issue into context. Less than 10% of breast cancers (and <15% of ovarian cancers) seem to be associated with BRCA1 or BRCA2 mutations. And, although even less common, there are hereditary breast cancers associated with other genes, so there might be a false sense of security from testing only the BRCAs.

And then there’s the uncomfortable fact that there have been over a thousand different mutations in BRCA1 and 2 discovered so far. You’d have to know which one to look for. Of course, some populations have more prevalent mutations –so called Founder effects– which might simplify the search. Two per cent of Ashkenazi Jews, for example, carry specific mutations of BRCA1 or BRCA2. And there are other populations carrying unusual founder mutations that might facilitate searches in them as well: people from the Netherlands, Quebec, Iceland, to name a few. Or in still other groups -some families, for example- if the particular mutation resulting in their tumours has been identified, then the process is obviously easier.

The most successful screening is in people with identifiable risks, however. With breast cancer, such things as family history -especially a young age of developing the breast or ovarian cancers (the younger, the more chance there is a risk that can be  inherited), or a family history of so-called triple negative breast cancers –progesterone, estrogen and HER2 receptor negative. Males with breast cancer (yes it happens) are another, albeit infrequent clue to increased risk.

But screening everybody? Let’s get back to risk assimilability. Just what risk is acceptable? Less than 50%? Less than 25%? No risk at all..? Sometimes the answer is easy: a 50-85% lifetime risk of breast cancer if specific BRCA1 or 2 mutations are present is likely not tolerable. But what about the odds if only 2% of the population had that risk, as is the case for BRCA1 and 2 mutations in the Ashkenazim? Or if the chances of those mutations are even lower: 1/800-1/1000 as it is in the general population?

And what if you are not a member of a high risk population, or if there are no cases of breast or ovarian cancer in the family? Should you still be screened? And if so, with what? Remember there are many different mutations possible on the BRCAs -not all of which may result in an increased cancer risk. And there are other genes than BRCA that may play a similar role sometimes. So if you are just concerned that you might be at some risk, or worse, merely curious… Well, its best to remember that we are all exposed to dangers each day that we don’t even think about -and there’s no avoiding them: everything from tripping and falling down the stairs, to slipping on some ice; from having a heart attack, to getting hit by a car crossing the street to shop. We have to put things in perspective: life is a risk, and we are fragile creatures. Remember Shakespeare’s Hotspur in Henry IV:

‘Tis dangerous to take a
cold, to sleep, to drink; but I tell you, my lord fool, out of
this nettle, danger, we pluck this flower, safety.

So, if there is reason to believe there is a risk on the horizon, then it’s best to mitigate it. But don’t go looking for it in places it doesn’t exist.