The Silent Killer - like Hypertension

MCI is a silent killer; you do not die of MCI; you die of something else
but at a rate to 2 or 3 times the normal mortality rates.
Why is MCI not a cause of death?   Why do not caregivers take this disease more seriously?

Dear Dr Caregiver

I am working as patient advocate for my wife, Carole B.(DOB: 05/20/1935). We want to thank you and your associates for the wonderful care provided to Carole. The breast cancer was identified in situ, the surgery was successful and post-operative care was magnificent.  Carole is still cancer free after three years.

Based on new findings by the Society of Actuaries, which show the mortality hazards of early stage MCI to be far greater than thought, and in Carole’s case about 323% higher than normal mortality, and about 300 times the risk of breast cancer;  I believe it is in Carole's best interest to treat her primarily for MCI and stop the treatment for Femara which studies show that is negatively impacts cognitive functions.  We look forward to our visit with you in a few weeks.

joe brophy

fellow, society of actuaries




Carole has been treated for Breast Cancer with Femara for about 3 years after very successful surgery (in situ) by Richard J. Barth at DHMC.   Her quality of life, however, is deteriorating.  She remembers little, cannot recall movies just seen within hours, can never remember the date, has trouble working gadgets, has difficulty starting and stopping the car, has difficulty with recipes and so forth and is always tired.   In the NOW she is fine.

Dr. Laurence J. indicates that there is no evidence of dementia from the three brain scans taken 2.5 years ago.  Her diagnosis is mild cognitive impairment (MCI). 

Having watched Carole carefully every day for the past three years, I observe that her ADL (Activities of Daily Living) is progressively becoming limited, and that she cannot focus.  Carole calls it Brain Fog; I call it chemo brain. I see no evidence the dementia suffered by her mother [which appeared immediately after open heart valve surgery] who died ten years after the heart surgery at age 92;  Carole’s father died quickly at age 77 of  colon cancer.

I just read a study by the Society of Actuaries, involving 6.2 million exposure years, which was indexed to the Medicare Database, and links significantly higher mortality with the “early stages of MCI.”   The study shows that people with MCI experience a 169% greater mortality hazard than people cognitively intact.  The mortality hazards are even greater for people with dementia and Alzheimer’s.

The mortality hazard is another 68% higher for people with at least one limited ADL.  Females fare better in the study by 32% compared to males, but mortality increases 12% with each year of age.  Making the actuarial adjustments for Carole, at age 79, she will experience increased mortality hazards at least 323% greater than a normal white female age 79.  At age 80, Carole’s normal expected life span for a white female should be 9.4 years.  The MCI hazard would reduce her life span by at least one-half.

[Source: The Relationship Between Cognitive Impairment and Mortality Rates Among Long-Term Care Insurance  I am waiting to hear from Dr. Marc Cohen who conducted the study to ascertain the age distribution within the study so I can refine my calculations. Answer: average age = 70]

The absolute risk of breast cancer represents about 1.25% of the mortality hazard among white females.  The absolute risk of breast cancer in situ hopefully should be significantly less but I have no data as yet. On the other hand, having had cancer, the risk of a second occurrence should be greater than 1.25%.  My guess it is 3.75% but I still need to verify this estimate.

I am concerned in my research when I read  “people eventually die of chemotherapy.” 

Unfortunately the microbiology of cancer and chemo is still not well understood.  The decision makers in the trial studies focus too much on hazard ratios rather than absolute ratios, particularly when the data sets are small which they usually are.

In any event the mortality hazards associated with MCI dwarf the cancer risks by a factor of about 300.


I plan to discuss my findings and concerns at our next visits with Carole’s caregivers in a few weeks.  I believe we should stop the Femara, at least for one year, unless there are proven alternatives, and rely on mammography.   Instead, Carole should be treated for cognitive impairment, in my opinion, caused by the Femara.  I need to find a proven program for MCI with or without medication.

Here are some data:

Population Mortality

q75 = 0.02681 = probability of a white female age 75 dying in one year.

q80 = 0.04487 = probability of a white female age 80 dying in one year.

q85 = 0.07763 = probability of a white female age 85 dying in one year.

q80-85 = .25133 = probability of white female age 80 dying in five years.

e80 = 9.4 years = life expectancy white female age 80.

Age Adjusted Death Rate = 0.006343 = year 2010 white females

Ratio of Crude Rate to AAD Rate = 798.7/746.2 = 1.070

Age Adjusted Death Rate – c00-c97, white female, malignant neoplasms = 0.001231

Death rate, white females, Ages 75-84, malignant neoplasms c00-c97 = 0.00596

NVSR 2010 TABLES:  AADR all causes = 983.8; malignant neoplasms = 172.5 = 17.5% of mortality; C50 breast cancer = 12.3 = 1.25% of mortality.

[The ABOVE are absolute measurements taken from US Tables 2008 thru 2011 National Vital Stat Reports.  There are hundreds of mortality tables to choose from, and the choice is not really relevant to my arguments.

Breast Cancer Statistics - Survival

Probability of dying in five years from Stage 0 (in situ) breast cancer ranges from .00 to .07 depending on the Breast Cancer internet source.  Of course, this is at variance with population mortality.  These data are factoids and pretty much useless except for general education.

Severity by Age: while breast cancer is less common at a young age (i.e., in their thirties), younger women tend to have more aggressive breast cancers than older women, which may explain why survival rates are lower among younger women. According to the American Cancer Society, 95% of new cases and 97% of breast cancer deaths occurred in women 40 years of age and older; per American Cancer Society.

Probability of dying in from breast cancer = .000385 aprx crude rate in UK

.00142 aprx crude rate x .634 (adjustment crude to age adjusted age rates) = 0.000244

Probability of dying (ages 75-84) = .00141

Probability of dying (ages 80-84) = .00167

The age adjusted rate represents  3.84% of white female population mortality (ages 75-84). Different tables can be used without impacting my findings.

Calculated by Brophy from: [Table 2.1: Breast Cancer (C50), Number of Deaths, Crude and European Age-Standardised (AS) Mortality Rates per 100,000 Population, UK, 2010; per Cancer Research UK]

Statistical Traps: Relative vs. Absolute Risk.  In a trial involving 10,000 women over 10 years, 30 are expected to get breast cancer during the trial duration. When all 10,000 people are put on a drug therapy, only 15 get breast cancer.  The RELATIVE risk reduction is 50%.  Looked at from a different angle, the risk of cancer is double if not taking the drug therapy. The ABSOLUTE risk is reduced from q= .003 to q=.0015 or by 0.15%. The drug may help 0.15% of woman but its side effects create increased risks to all 10,000 women who have taken the drug therapy, even if that harm is not immediately evident. The samples are not large enough to test the side effects.  If only 1% of the 10,000 suffer a significant side effect, then 100 women suffer a significant side effect compared to 1.5 who suffer cancer.    Source: Joe Brophy.

Femara and Cognition:  Endocrine therapy for breast cancer may affect cognition.  For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment. [measured using standardized tests one year after treatment.] There are numerous studies linking chemo and cognition. Source:

Joe Brophy FSA, 2/16/2013


Audit trails and notes

Joe:  On the FDA website ( they have femara’s new drug application (NDA):

I started looking thru the data and there is a lot there.  Doesn’t look like there are large studies, but hopefully what you need is there. There is also a Freedom of information act (FOIA) to get more info:

If the FDA doesn’t have the data, sometimes you can contact the company (Novartis) to get that info:  If they won’t give it to you, I can contact them and see if being a pharmacist would help to get the info.

I was trying to get any information on adverse effects reported to the FDA on MEDWATCH (a system where anyone can report adverse effects on drugs) but it said I had to fill out the FOIA to get info on femara.

I also talked to our oncology pharmacy specialist and she said that oncologist’s use femara’s class of medications because the alternative, tamoxifen, has more cognitive effects – she called this “Chemo Fog” instead of “Chemo Brain”.  The theory behind cognitive issues was interesting to me: these drugs block estrogen receptors and estrogen is involved in processes in your brain also.  Her thought was (based on the info you gave me) that after 3 years, the risk of the drug probably outweighs the risk of breast cancer recurrence as long as she is followed closely, especially due to your concerns. 

I went to a talk on side effects ~5 years ago and something the presenter said has stuck with me ever since “Even if a serious side effect is “RARE”, if you are that “RARE” patient, is it very significant to you”.  I found a lot of the studies that you have found and to me it seems plausible that the femara may be contributing.

I hope this helps and that we can help Carole.  Let me know anything else I can do to help.

Jeff Fish


From: joseph brophy []

Sent: Sunday, February 10, 2013 9:33 PM

To: Fish Jeffrey T

Cc: 'kathleen fish';

Subject: FW: patient Carole A. Brophy - femara and chemo brain

Jeff Fish; here is a draft of a letter that I eventually want to send to the five doctors mentioned at the end; they are all listed at the end. I am absolutely convinced that Carole has chemo brain.  But I do not want to piss off all the doctors with by big mouth. I need to do a little more fact finding.  Maybe you can point me in the right direction.  Joe<><><><><> [jeff is a family member, pharmacologist, a clinical instructor, and program director of critical care)

tom brophy sr health professional, cfo, treasurer blue shield

kathleen brophy fish, sr health professional and actuary

mark fish, sr health professional, coo and actuary

Gregory Burke MD PhD oncologist microbiologist drug researcher professor, surgeon, friend

Dad I agree very much with Kathleen that instinct is huge. Interestingly we all know that mom has never been one to take medications lightly. She feels that the estrogen replacement that she took during menopause is what put her at risk for this breast cancer event in the first place. Back when she was taking the estrogen she challenged the doctor but ultimately continued with the therapy. I believe it is now known these patients, such as mom, were put at a higher risk for breast cancer. It makes sense to me and I would support your decision to stop the femara. I found Jeff's comments very interesting. I also think mom would completely agree if she was of better sound mind. Nanna Eleanor's dementia was brought on dramatically after she experienced anesthesia psychosis at NYU. I guess our genes are very much at high risk for dementia.  Good job Dad.  The doctors providing her care should not be offended. Maybe they will learn something new of they look into your questions. Maureen

Dad, you are amazing.  If I were a doctor I would bow to you.  Your research is very impressive therefore I would be surprised if they challenged you.  Either way, you really only have to convince Mom not necessarily the doctors.    We are a highly over medicated society.  While your research is sound, gut instinct is worth a lot too.  Doctors are too tied to evidence based decisions.  Jeff, thank you so much for taking time to help my parents with this.  Your help is invaluable. Kathleen

 Dad: I agree that you should have this conversation with the doctor and you have done a good job of supporting your case statistically. Editorially I would only suggest you state you ask in the first paragraph.....something like.... I believe it is in Carole's best interest to treat her primarily for MCI and stop the treatment for Femara which might be negatively impacting her cognitive functions.  Tom

PAPA: Every patient needs an advocate.  My two cents towards the admirable job you are doing as Carole's advocate:  I agree with Tom's recommendation that you put the "ask" at the beginning of the letter.  Let the docs  know right away what you want.  The way I read it, you are making a two-pronged argument leading to the conclusion that Carole should stop taking Femara.   1:  Taking Femara is Lowering Carole's Quality of Life.  2:  Taking femara is Decreasing Carole's Life Expectancy.
Your narrative provides compelling support for argument # 1 but it is intertwined with your equally compelling data analysis in support of #2.  I found I had to read your letter a couple of times to sort it out.  You might consider putting some of the data analysis in an addendum.  The docs will recognize that you know your stuff and have strong support for your request. I have a specific question regarding your letter.  Shortly after your sentence, "In any event the mortality hazards associated with MCI dwarf the cancer risks by a factor of 300," you say that Carole should be treated for severe cognitive impairment yet in paragraph three you say that her diagnosis is MCI or mild cognitive impairment.  Are you saying that Carole's impairment is moving beyond mild and into severe?  Whatever the word you use, I think you should also close the letter with your request -- another argument for putting some of the data analysis in an addendum.  In reading others' responses I was reminded of the book Carole gave each family for Christmas a few years ago, "My Mother, Your Mother" by Dennis McCullough, M.D.  Carole's endorsement of that book confirms that you are on the right track.  I will bet that she remembers the book.  We will be very interested to hear the outcome.  Jane

Hi Joe,  Thanks for your interests in the study. The average ages of LTCi applicants who were assessed by EMST  or DWR  are 64 and 71 respectively, and the overall average age is 70.  Regards, Xiaomei, Life Plans;  Xiaomei Shi | Senior Statistician, Research Department; P | 800-525-7279 Ext:291; F | 781-893-6905; 51 Sawyer Road, Suite 340, Waltham, MA 02453;;;,Chemo+Brain/?a=s,Chemo+Brain/?a=s


Brophy Wednesday 20 February 2013 - 11:06 am | | Brophy Blog

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