User talk:Veryverycavy

--Richiez (talk) 20:52, 3 February 2011 (UTC)

BRCA mutation
You have chosen a particularly difficult field for your first contributions to wikipedia so please take no offense if I revert most of them. What you write is not wrong, but totally misleading to the average reader. 90% reduction of cancer risk needs to be balanced with overall mortality. Richiez (talk) 20:57, 3 February 2011 (UTC)

Richiez, is this how I reply? I am a new wikiperson, so I am not sure how to correspond!

The risk of *getting* breast cancer is a different statistic than the risk of *mortality* from breast cancer. For clarity, the two need to be separated--hence the change in the first paragraph. I see that NCI states BRCA breast cancer risk is 60 percent, but I am frankly taken aback at this, because all the other sources I have seen---including my own genetic report---put the risk at closer to 90 percent.

I left the information about the mortality study; it is important. But I don't think the current version reads as balanced. Emphasis on that mortality study, put together with the understatement of the risk of breast cancer in the first paragraph and no mention of the grueling nature of cancer treatment, gives the impression that women who have prophylactic mastectomy have no good reasons to do so. In reality, the prospect of a lifetime of repeated cancer treatment, such as many of us have seen our mothers suffer, is a huge motivation. As is the financial impact of such treatment. Quality of life is a very important issue that must be taken into account.

There is a great deal of misunderstanding in the general population and the media about prophylactic mastectomy, in which women who do this are painted as sort of hysterical. The entry without balance contributes to this perception.Veryverycavy (talk) 19:49, 4 February 2011 (UTC)


 * Regarding 60 or 80% I am by no means religious about it, then again I see many sources not presenting a single number but rather a range like 60-85.. similar for OC. The reference should be some review or similar, mskcc only as last resort.


 * While the absolute incidence rates are important, they can give the wrong impression. Ovarian cancer seems to be the bigger threat despite lower incidence. Trying to find good numbers about all cause mortality of BRCA victims as I believe this is a good way to support someone trying to make a rational decision.


 * You are right about the impact of cancer treatment and cancer fear. On the other hand we must keep an eye on the future. If a 25year old undergoes PM today the effect will be small by todays standards and there is a good chance that within the time she reaches 40 the balance may flip more or less dramatically. The issue looks completely different if she is 40 today, under many circumstances it looks like the best option for these cases as of now. I am rereading the data from Kurian et al and hope to expand this into more detail, if it can be done in a readable way. No I did not realize there is some media frenzy about PM, this is unfortunate.. this has been different in different countries and different times. I am still under the impression that the positive effects of PM are strongly exaggerated in many places. Most people read it reduces BC rates by 90% and turn off rational thinking.


 * Some more things to do, things like tubal ligation for OC prevention might be interesting in the context of BRCA. Also I have seen information that some lifestyle factors may be even more important for high risk BRCA carriers than for the average population. On the other hand I am not sure I can find any high quality data on this and even if I find not sure how to put it into relation with the aforementioned mortality study. Richiez (talk) 22:07, 4 February 2011 (UTC)

Btw you might find Wikipedia talk:WikiProject Medicine useful. Richiez (talk) 22:26, 4 February 2011 (UTC)

I appreciate your rumination on all this. As you continue to do so, I still urge you to keep in mind that breast cancer mortality is not the only issue, or even perhaps the most important one in a sense. Here's one way to think about the options: Let's say for the sake of argument that a woman could be assured she would reach the age of 70, whether she developed breast cancer or not. Would she rather live without breast cancer, or with it? Given the prospect of almost certain cancer, she'll have to have the surgery anyway (and with fewer choices), plus chemotherapy, radiation, blowing through all her savings (IF she has health insurance at that point), straining her marriage, and causing trauma for her kids.

As with lifestyle choices, all the literature I've been able to find (I'm an avid runner and veggie-eater) indicates that the effect of diet for BRCA mutation carriers is statistically insignificant. However, as you know, this--as with the research on mortality, as well as on prophylactic mastectomy, since it's a pretty new practice--may change as new research is done and time marches on. Veryverycavy (talk) 22:51, 5 February 2011 (UTC)


 * ok, glad for your opinion. I am getting your point. Still under the impression that prophylactic mastectomy seems rarely advisable for women significantly younger than 40. In medicine total survival analysis is almost always the best guide but when there is only marginal difference there is obviously much room for interpretation. We have had that discussion (Talk:Breast cancer)about recent Cochrane reviews which (totally against intuition) concluded that current mammography guidelines for general population may in fact do more harm than good because of overdetection and overtreatment of cancers that would never become clinicaly significant. It is well possible that some of the 60-80% BRCA women who get breast cancer are result of similar overdetection, hence total mortality is an extremely important control. Supposedly most of the "overdetected" cancers would be grade I and not terribly invasive to treat, the data are not good enough to draw any conclusions about such speculations. Also, when 1 in 8 average women is expected to get breast cancer during her life is it really that much different than a 60-80% chance or in other words where do you draw a line when to recommend mastectomy. Fearmongering is a a great business model. Richiez (talk) 13:30, 6 February 2011 (UTC)

I am familiar with the new questions about mammograms for the general population; in fact I remember the value of mammograms being debated as long ago as the early '90s. It's quite interesting, and I do agree with you about fearmongering as a sales ploy! But as you know, the cost-benefit analysis for a woman without a BRCA mutation is a completely different one than that for a woman with a BRCA mutation.

Family history is also an enormous factor in a woman's decision-making process, since genetic analysis is not yet personalized. If a 25-year-old's mother and maternal aunt both got breast cancer by age 30, and especially if one or both of them died, then clearly breast cancer is a bigger risk for her than ovarian cancer, regardless of the statistics for BRCA1 or 2 mutations in general. If family members suffered from but survived breast cancer at a young age, and then had ovarian cancer in their 40s or 50s, then the 25-year-old still has a more urgent threat from breast cancer than from ovarian cancer, *at her age*.

A woman in her 20s with this kind of family history might have excellent reconstruction options available to her, especially if the mastectomy is prophylactic. And she is very unlikely to take tamoxifen or have an oophorectomy, since they would impact her fertility and sex drive. Believe it or not, losing the ovaries can actually be *more* difficult for some women than losing their breasts.

Bottom line: The section under prophylactic surgery reads as biased against prophylactic mastectomy, with the only criterion being mortality. As I've explained, this is incomplete. I'm not going to editing battle over it, because you will win. But it's really a shame.

Also, I am sticking to my statement that the NCI breast cancer risk figure of 60 percent in the first paragraph is grossly insufficient. If a range is most accurate to current knowledge, then we should state a range. One option would be to follow the NCI statistic with something like, "but many sources place it as high as 90 percent." As sources we have MSKCC and MD Anderson Cancer Center (which says 40 to 87% lifetime risk in a 2009 document called "Hereditary Breast and Ovarian Cancer Syndrome"). It seems to me that the top cancer research institutes in the country would be at least as reliable as a government agency. In a quick search I didn't find a particular review study, but rather assume that the figures given by the institutions, which oversee the research, are based on such reviews.

Just trying to broaden understanding...

I think it's interesting to consider whom we imagine to be the readers here. I'm guessing you might imagine readers to be women who have found out they have a BRCA mutation, and you don't want to alarm them. I imagine them more to be friends and family of those women, students writing research papers for school, etc., and I want these readers to be able to understand the position of women in this situation. In truth, our readers are both.

Veryverycavy (talk) 22:01, 6 February 2011 (UTC)


 * Familly history is an important factor but I have briefly researched a few "rare" breast cancers such as inflammatory breast cancer and secretory breast carcinoma (which accounts for >50% of pediatric cases) which are publicly known as affecting "especially young women" and realized that breast cancer incidence in general for younger patients is exorbitantly low - while the gap in public perception of perceived and real age distribution of such cancers is exorbitantly large. I would not be surprised if the same were true for BRCA.. and whichever way it is the numbers are so low that it will be hard to find anything but anecdotic reports. There are some statistics for ages 30+ but not much bellow that age.. iirc 0-30 accounted for 0.5% of all breast cancers, BRCA or not.


 * Yes, I am fully aware that oophorectomy is the more serious surgery. It has vastly negative effect on survival when done without proper indication such as BRCA1, even when done postmenopausaly in women as old as 70. Incidentally ovarian cancer is much more likely to strike younger women than breast cancer although I am not sure of the same holds for BRCA related ovarian cancer.


 * Having said that, I will look again if I can find some reasonable information and I will certainly make sure to emphasize the psychological aspects of PM. I do not have much time to do any more complicated changes this week unfortunately.


 * As of references it will be easy to find something, on a subject like this I prefer to see the primary source of the information published in a medical journal indexed on pubmed. Whatever cancer institutes publish on their home pages, they publish it also in the medical journals and this kind of publications is almost always more reliable as it carries a clear date of publication, more precise list of references and was better reviewed.


 * Finally, wikipedia should be pretty much reader-agnostic. Ideally students, researchers and patients would all find interesting information here. Richiez (talk) 23:56, 7 February 2011 (UTC)

While I don't have statistics, I have met numerous BRCA+ women whose relatives developed breast cancer before the age of 30 (and in fact I am one of those women). I don't intend to dwell on age as an issue, just to make the point that there might be very rational reasons why a woman of any age might choose prophylactic mastectomy. In fact, based on what I have heard from other women and from doctors, most women with BRCA mutations *don't* elect prophylactic mastectomy, but go with screening. So, when a woman *does* choose surgery, it is likely to be because she has immediate personal experience and family history that have made a profound impression on her, and are completely valid factors in her decision-making.

You said, "I am still under the impression that the positive effects of PM are strongly exaggerated in many places. Most people read it reduces BC rates by 90% and turn off rational thinking." I don't think this is a good reason to omit the 90% figure. Your definition of "rational thinking" is certainly not necessarily someone else's definition of "rational thinking."

Don't worry--I'm busy too! I think it's great you spend so much time on this.


 * What do you think about this and this graphics?Richiez (talk) 20:59, 8 February 2011 (UTC)

I think it's a very informative analysis. Of course, it is based on a computer model, not by actually following women until the age of 85 (there just hasn't been enough time yet, since prophylactic mastectomy has been practiced). So, it is new data, and unique. Nevertheless, given the aggressive screening regimen (which is also relatively new, along with the knowledge of the genetics in the first place), perhaps it will play out to be supported by further studies.

Regardless, I have no argument about the mortality data. My argument is about focusing too narrowly on mortality alone. Thirty years ago when my mom had her first breast cancer, we predicted that treatment would be very different by now...and it really isn't. Mom is still alive, I am fortunate to say (and still in cancer treatment). Yet I chose to have prophylactic mastectomy anyway, based on her miserable experiences and the mutilation to her body, both inside and out. And residual effects on her mind as well. Living isn't such a prize when life is hell, you know? As I said when planning my own PM: "I am not afraid of dying; I am afraid of cancer treatment." Veryverycavy (talk) 17:24, 9 February 2011 (UTC)


 * yes, I understand that aspect. The survival information is just the basis of everything else and the first thing that must be correct - for example it must be clearly stated that an oophorectomy that is not strictly indicated or done too early will result in reduced overall survival. I have done a few changes to add more detailed data in a comprehensible way and will expand and polish it further. The psychological effects will come next.


 * Another reason for the survival data is that it the dataset of Kurian et al is very complete and robust, the most recent and best I could find. They have examined what happens with their predictions if breast cancer rates are modified eg by 30% and collected a lot of valuable data in a consistent way. It turns out, survival rates are relatively robust against variations in a lot of factors. If you find anything in this paper that you think deserves extra mention let me know.


 * I have not yet looked at the exact cancer rates in detail, my impression is that there is wide variation because many sources report conditional probabilities, eg probability under the assumption that the person does not die of any other cause before that. This needs to be interpreted (and explained in wikipedia) with some caution because disregarding other mortality beyond a certain timespan can be misleading. Anyone who would not die of any other cause would probably die of breast cancer after some (long) time, the incidence is simply accumulating year by year as far as we know today.


 * Also, do not forget to sign your posts even if it is your talkpage, very helpful if someone else would like to look at this discussion. Richiez (talk) 13:25, 9 February 2011 (UTC)

I'm glad to see the statistics in the first paragraph are more complete now. I noticed a few typos and such and I'll fix those. Also, I'm going to rephrase "a healthy 25-year-old woman" under Survival Impact, because it implies a BRCA+ woman is necessarily unhealthy.

I'm curious about the Environmental Factors section. I don't understand how researchers came up with a sample of BRCA+ women from a time before we knew BRCA existed--? (I wasn't able to view the study.) Also, I am highly skeptical that this one study should form the basis of a conclusion.

One more thing: I'm uncomfortable with making the statement "Prohpylactic mastectomy has only a very small risk while oophorectomy has substantial adverse effects"---especially twice. For one, saying there is a "risk" is very vague; risk of what? It can be risk to life, risk of developing cancer, even risk to one's self-image. Also, we don't back that up in any way that I can see. (Interestingly, from my experience and those of the BRCA+ women I know, doctors usually recommend salpingo-oophorectomy almost immediately, as a rather annoying knee-jerk reaction to finding out a patient's BRCA+ status.) Anyhow, I don't have time to pursue it at the moment and don't feel strongly enough about it to change it right now; I just wanted to share my thoughts. Veryverycavy (talk) 18:49, 14 February 2011 (UTC)


 * Hi again. Regarding statistics, it looks like I will have to rephrase that again. The evidence for the high breast cancer risk with BRCA2 is conflicting and confusing and because only one in 20 studies published something like a "lifetime risk" we will have to content with age-70 risk all the way I am afraid. I am currently reading the Antnonioni paper which is freely accessible when you register and has a nice overview of all other results that have been reported.


 * The pre/post 1940 development has been confirmed by at least one other study, non-BRCA breast cancer has seen a similar rise and it is consistent with the assumptions of several protective (early primiparity and breastfeeding) and adverse (nuliparity, hormone use) factors. The interesting part would be to learn more about the effects of the single factors.. if there is data available. Ovarian cancer risk also decreases with number of pregnancies btw. Healthy 25 year old: they are of course both healthy.


 * Regarding risk of oophorectomy, it seems not a good thing to recommend before age 40. The women face substantially increased cardiovascular mortality, bone and other problems. The problems are still bad enough when done at 40, still measurable when done at 65(!) and of course much worse at a substantially younger age. The details are at oophorectomy although for the BRCA article it suffices that Kurian et al do not recommend it before 40. The rate of ovarian cancers is very small before 40 (look into the Antonioni paper), oral contraception may provide up to 80% risk reduction in this group and tubal ligation 60% (would be nice to know if they add up; there is only early indication that this factors are also valid for BRCA cases). Oral contraception though is suspected to raise breast cancer risk in high risk BRCA mutation carriers. PM has a certain rate of surgical complications and a certain rate of psychiatric complications but no long term effects on mortality like oophorectomy. Unlike oophorectomy the risks of PM are basically the same whether its done at 30 or 50. Richiez (talk) 21:10, 14 February 2011 (UTC)