BRCA BREAST CANCER MUTATIONS & MRI SCANS

An estimated 5-10% of all breast cancer cases are associated with an inherited mutation in either the BRCA1 or BRCA2 genes.  In addition to conferring a 50-85% lifetime risk of breast cancer, inherited mutations in either of these genes are also associated with a 20-60% lifetime risk of ovarian and peritoneal cancer as well.  (As this gene mutation can be passed down to both men and women, men can also be affected by BRCA gene mutations, and they may experience an increased risk of breast and prostate cancer.)  Current breast cancer screening guidelines for women with BRCA1 and BRCA2 gene mutations include the early use of annual mammograms (starting between 25 and 30 years of age, instead of age 40, as is the case for the general public) and frequent clinical breast exams. 

Recently, the American Cancer Society and other breast cancer advocacy groups have suggested that MRI scans of the breast should also be added to annual mammograms, in an effort to detect breast cancers at an even earlier stage than is usually possible with mammography alone.  However, MRI scans, like mammography, have their limitations and drawbacks.  First of all, MRI scans are far more expensive than mammograms, and many healthcare analysts have rightly asked how our already grossly under-funded healthcare system will be able to absorb the added cost of expensive breast MRI screening exams.  Secondly, breast MRI, like all clinical tests, is not perfect.  Current generation MRI machines and computerized imaging software can accurately detect pre-invasive and invasive breast cancer in more than 90% of cases (as opposed to mammography’s 80-85% overall accuracy, and its even poorer sensitivity in young women with dense breast tissue).  However, MRI’s higher degree of sensitivity and overall accuracy is achieved at the expense of specificity.  MRI is currently associated with a “false negative” rate of 10-30% percent, unfortunately.  This means that for every 100 women who have an abnormal breast MRI test, somewhere between 10 and 30 of these breast abnormalities will ultimately be determined to be benign lesions of the breast, rather than cancer.  Additive to the economic costs of MRI as a breast cancer screening tool, therefore, are the economic, physical and emotional costs associated with the many women who must undergo biopsies of breast abnormalities identified by MRI that turn out, in the end, not to be cancer after all.

A new Canadian study, from Toronto, just published in the journal Cancer Epidemiology Biomarkers & Prevention, takes a closer look at the diagnostic value of mammography in younger women with BRCA1 and BRCA2 gene mutations, and the role of both mammography and MRI scans in screening young women with these hereditary breast cancer syndromes.  In this small study, 42 women with a recent diagnosis of pre-invasive or invasive breast cancer, and with known BRCA gene mutations, underwent computer-assisted measurements of their breast tissue density.  The average age of these participating women was 48.  The women were then grouped according to their breast density measurements, and were then subjected to both mammography and breast MRI imaging.

The findings of this study were in general agreement with similar previous studies, and confirmed that women with denser breasts (as is common in young, premenopausal women) are less accurately screened for breast cancer by mammography alone.  Overall, the sensitivity of mammography alone in the women participating in this study was a rather dismal 20% for pre-invasive breast cancer (ductal carcinoma in situ, or DCIS) versus 87% for MRI alone.  Among patients diagnosed with invasive breast cancer, the sensitivity of mammography alone wasn’t much better, only 26%, while the sensitivity of MRI in detecting invasive breast cancer was 90%.  Importantly, this small study determined that even among women with less dense breasts, mammography was still significantly less sensitive in detecting DCIS and invasive breast cancer than MRI. 

Several recent studies have confirmed that MRI is more sensitive in detecting breast cancer, and at an earlier stage, than mammography alone.  Given the complex and still unclear clinical and economic “risk-to-benefit” associations involved with breast MRI, the indications for breast MRI screening will continue to be debated for some time.  At some point, given the enormous cost associated with the more routine use of breast MRI, there will have to be some solid clinical data showing that the added sensitivity of MRI in detecting early breast cancers translates into meaningful clinical and societal benefits.  However, increasingly, screening MRI of the breast is becoming the de facto imaging standard of care for women with BRCA gene mutations (and the few other gene mutations that have been associated with familial breast cancer, as well), and for women with a personal history of breast cancer or a strong family history of breast cancer.  It remains to be seen, however, whether or not the current indications for screening breast MRI will someday be expanded to include the general public.  I predict that, eventually, the indications for routine annual MRI breast cancer screening will indeed be expanded to include the general public, but not before more substantial high-quality clinical research data comes along to prove that, despite the high cost of MRI, it is still a cost-effective public health screening tool from both clinical and economic perspectives. 

 

BLADDER CANCER PREVENTION WITH BROCCOLI?

An estimated 75-80% of all cancers in the United States can probably be prevented by lifestyle changes alone, according to many public health experts (this is a major theme of a new book that I am currently writing).  Given the enormous potential of achievable cancer prevention strategies to reduce the incidence of cancer in our society (i.e., relative to the important but very incremental survival gains that we are making with improved screening and treatment interventions), cancer prevention is an area of great interest to me.  Along these lines, a new study in the journal Cancer Research looks at the effects of broccoli sprouts on the development of cancer of the bladder in laboratory rats.

According to the American Cancer Society, nearly 70,000 new cases of bladder cancer will be diagnosed in this country in 2008, and an estimated 14,000 people will die of the disease.  When discovered early, bladder cancer is highly treatable and often curable.  In its later stages, bladder cancer often requires radical surgery for treatment, and as with most cancers, cure rates decline with advancing stages of disease.

The so-called cruciferous vegetables (e.g., watercress, Brussels sprouts, broccoli, cabbage, bok choi, kale, horseradish, radish and turnips) contain high concentrations of isothiocyanates, which have been shown, in numerous research studies, to have potential anti-cancer properties.  Broccoli sprouts, in particular, have very high concentrations of isothiocyanates. 

Previous research, relying mostly upon cell cultures and laboratory animals, have suggested that isothiocyanates may be capable of shutting down important biochemical pathways associated with cancer cell development and growth, as well as activating other biochemical pathways that are associated with cancer cell “suicide” (apoptosis).  Some research studies have also suggested that isothiocyanates might also increase the activity of enzymes in the body that “detoxify” many of the cancer-causing substances that we commonly ingest or inhale. 

This study was jointly carried out by researchers from the Roswell Park Cancer Institute in Buffalo, the Johns Hopkins University in Baltimore, and Massey University in New Zealand.  Using an established rat model for bladder cancer, feeding the animals a freeze-dried extract of broccoli sprouts was observed to significantly inhibit the development of bladder cancer.  Additionally, levels of enzymes known to detoxify cancer-causing substances increased with increasing doses of broccoli sprout dietary supplementation.  More than 70% of the ingested isothiocyanates were also found to be excreted into the urine of these animals, and high levels of isothiocyanates were also found within cells lining the bladder as well.

This study shows that, at least in one animal model of bladder cancer, broccoli sprouts appear to have significant and potent cancer prevention properties.  Other studies have shown similar anti-cancer properties as well.  Unfortunately, while there are a couple of ongoing human clinical research trials looking at the effects of dietary isothiocyanates on the prevention and treatment of prostate and lung cancer, there has been very little in the way of prospective, randomized human clinical trials with dietary isothiocyanates.  Therefore, it remains unclear if the anti-cancer properties of dietary isothiocyanates seen in a Petri dish or in laboratory animals will actually translate to humans as well.  However, given the lack of apparent side effects associated with naturally-occurring sources of isothiocyanates, it seems reasonable to include them within a well-balanced low-fat, high-fiber diet for now, and until high quality prospective clinical trials definitively assess their risks and benefits in humans.

 

DIABETES: RISK OF DEATH DUE TO HEART ATTACK & STROKE

It has long been known that diabetes is associated with an increased risk of cardiovascular disease, and that diabetic patients often develop coronary artery disease, heart attacks, strokes and peripheral vascular disease at a younger age than people without diabetes.  However, the true extent to which diabetes alters the risk of cardiovascular disease has not been consistently evident from prior research trials.  A new, very large Danish public health study in the journal Circulation provides new information regarding the degree of cardiovascular disease risk associated with diabetes, especially among younger adult patients.

In this study from Copenhagen, 5 years of data from a national public health registry was used to assess all residents from Denmark who were 30 years of age or older.  This study specifically compared death rates due to cardiovascular disease between patients receiving medications for diabetes and patients with and a history of heart attack (myocardial infarction) but without a history of diabetes.  Both groups of patients were then compared with otherwise healthy, age-matched patients without a history of diabetes or myocardial infarction.  Nearly 72,000 patients with diabetes were included, as well as almost 80,000 patients with a prior history of myocardial infarction (but without a history of diabetes). 

When men with diabetes were compared with men without diabetes (but with a prior history of myocardial infarction), the risk of death due to cardiovascular disease in each group, as compared to non-diabetic men without a history of myocardial infarction, was strikingly similar.  During the 5-year course of this study, the diabetic men experienced 2.4 times the risk of cardiovascular death when compared to their same-age peers without diabetes or a history of myocardial infarction.  Likewise, the non-diabetic men with a prior history of heart attack experienced a 2.4-fold increased risk of cardiovascular death when compared to healthy same-aged male peers. 

When women were studied, the results were essentially the same.  Diabetic women had 2.5 times the risk of cardiovascular death when compared to non-diabetic women without a history of myocardial infarction, while non-diabetic women with a history of heart attack faced a 2.6-fold increased risk of cardiovascular death when compared to their healthy same-aged female peers.

Taken together, this excellent and very large public health study really puts into perspective the additive risk of cardiovascular disease (and death due to cardiovascular causes) associated with diabetes, even in relatively young adult patients.  Essentially, a diagnosis of diabetes, even without a prior history of cardiovascular disease, appears to put such patients at an equivalent risk of death due to cardiovascular disease as is seen in non-diabetic patients with a documented prior history of coronary artery disease and a heart attack. 

The incidence of diabetes, which is a systemic disease that often affects virtually every organ in the body, is dramatically rising in tandem with the exploding incidence of obesity in our society.  In addition to more aggressive efforts at diabetes prevention, the results of this important study suggest that more aggressive cardiovascular disease prevention, screening and treatment efforts should be directed at patients with diabetes, including young and otherwise healthy patients with diabetes.  As with cancer, it appears that the majority of adult-onset cases of diabetes could probably be prevented with healthy lifestyle approaches, including a healthy low-carbohydrate, low-fat, high-fiber diet; plenty of exercise; and the avoidance of obesity. 

Prevention remains a far more effective intervention against the development of both diabetes and cancer than any “after the fact” treatment options available to us today….

 

Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at:  rwascher@doctorwascher.net
 

http://www.doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

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