One-third of all cancers maybe inherited

Muci et al published in JAMA the results of a trial that suggests that approximately one-third of all cancers are due to inherited genes. 

The investigators looked at data from 80 309 monozygotic and 123 382 same-sex dizygotic twin individuals (N = 203 691) within the population-based registers of Denmark, Finland, Norway, and Sweden, who were part of the Nordic Twin Study of Cancer. 

Twins were followed up a median of 32 years between 1943 and 2010. There were 50 990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up.

The main outcome was incident cancer and time-to-event analyses were used to estimate familial risk.

A total of 27 156 incident cancers were diagnosed in 23 980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type.

The analysis of data found that overall heritability for cancer was 33 percent among the entire study population, and significantly higher for certain types of cancers.  Significant heritability was found in 58 percent of diagnosed skin melanomas, 57 percent of prostate cancers, 43 percent of non-melanoma skin cancers, 39 percent of ovarian cancers, 38 percent of kidney cancers, 31 percent of breast cancers and 27 percent of uterine cancers.  In the same study researchers identified a set of cancers in which genetics play a very small role. This group includes lung cancer (18 percent), colon cancer (15 percent), rectal cancer (14 percent), and head and neck cancer (9 percent).”

In this long-term follow-up study among Nordic twins, there was significant familial risk for cancer overall and for specific types of cancer.  This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

Top Three Posts

During the last two years I uploaded 20 posts in my blog Medical News Monthly.  The top three in order of viewing frequency were:

1.     Ebola Outbreak

http://medicalnewsmonthly.blogspot.com/2014/08/ebola-outbreak.html

2.     The Mediterranean Diet

http://medicalnewsmonthly.blogspot.com/2014/07/the-mediterranean-diet.html

3.     WHO Report on Antimicrobial Resistance

http://medicalnewsmonthly.blogspot.com/2014/05/who-report-on-antimicrobial-resistance.html

Most of the visitors were from the United States, followed by Greece, Russia, France, Macedonia, Poland, Ireland, Ukraine, Germany, Switzerland and India in that order.

SPRINT trial redefines blood pressure targets

More than 70 million people in the United States suffer from hypertension – which presently is defined by a systolic blood pressure of higher than 140 mm Hg and a diastolic of higher than 90 mm Hg.  A landmark study called SPRINT (Systolic Blood Pressure Intervention Trial) challenges the accepted guidelines of optimum level for systolic blood pressure and provided information about benefits and shortcomings of intensive pharmacotherapy. The study was published in NEJM was interrupted nearly two years early, when it became apparent that lower blood pressure for most people over 50 prevented heart problems and deaths.

In the SPRINT trial, 14,692 patients were assessed for eligibility, and 9361 individuals with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, were randomly assigned in two groups; a systolic blood-pressure target group of less than 120 mm Hg (intensive treatment) or a target group of less than 140 mm Hg (standard treatment).

The primary outcomes were myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.

At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The mean number of blood-pressure medications was 2.8 in the intensive-treatment group and 1.8 in the standard-treatment group.  The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003).

Investigators found that there were 27% fewer deaths (155 compared with 210) and 38% fewer cases of heart failure (62 compared with 100) among patients who achieved the systolic pressure target of 120 mm Hg than among those who achieved the current 140 mm Hg target.

The lower relative risk of major cardiovascular events observed across subgroups defined according to age, sex, race, medical history, and baseline blood pressure among patients who achieved the systolic pressure target of 120 mm Hg in comparison to those who achieved the currently recommended level of 140 mm Hg.

Rates of serious adverse events of hypotension, syncope were 67% and 33% higher in the intensive therapy group.   Electrolyte abnormalities, and acute kidney failure were noted but injuries due to falls surprisingly were not more common, as had been feared among the elderly in the intensive-treatment group.

The research indicated that among patients over 50 at high risk for cardiovascular events who are not diabetics, targeting a systolic blood pressure below the current guidelines of 140 or 150 mm Hg to less than 120 mm Hg, prevented heart disease and strokes and thus save lives.

DOI: 10.1056/NEJMoa1511939

Breast Cancer Screening for Women at Average Risk

Breast cancer is a leading cause of mortality among US women.  About 200,000 women are being diagnosed every year in the US with breast cancer and 40,000 women die from the disease.

Despite the interest and research on breast cancer screening, there is uncertainty about mammography’s benefits versus potential harms from false positives and overdiagnosis.  Thus recommendations on the frequency of its use are wide-ranging.  Different countries and professional societies have guidelines recommending from annual to biennial to triennial or no screening at all.   

In 2003, the American Cancer Society (ACS) recommended annual mammography screening for all women starting at age 40 years and continuing as long as a woman remained in good health.  The ACS also recommended clinical breast examination (CBE) periodically for women in their 20s and 30s and annually for women 40 years and older.

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The ACS has revised its guidelines regarding when and how often women at average risk should receive screenings for breast cancer.

The ACS commissioned a systematic evidence review in 2015 of the breast cancer screening literature and a supplemental analysis of mammography registry data to address questions related to the screening interval.

 Formulation of recommendations was based on the quality of the evidence and judgment about the balance of benefits and harms such as biopsies resulting from false positive mammograms.

Screening mammography in women aged 40 to 69 years is associated with a reduction in breast cancer deaths to as much as 30 percent, and inferential evidence supports breast cancer screening for women 70 years and older that are in good health.  Evidence does not support routine clinical breast examination as a screening method for women at average risk.

Oeffinger et al review and analysis are described in their paper in JAMA and form the basis of the new ACS recommendations that are:

·      - Women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation).

·      - Women aged 45 to 54 years should be screened annually (qualified recommendation).

·     -  Women 55 years and older should transition to biennial screening (strong recommendation).

·     -  Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation).

·     -  Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (qualified recommendation).

The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation).

These updated ACS recommendations bring it closer to the draft guidelines released on April 20, 2015, by the U.S. Preventive Services Task Force (USPSTF) for breast cancer screening which are:

·      For women at average risk for breast cancer, most of the benefit of mammography will result from biennial screening during ages 50 to 74 years.

·      Of all age groups, women ages 60 to 69 years are most likely to avoid a breast cancer death through mammography screening.

·      Screening mammography in women ages 40 to 49 years may reduce the risk of dying of breast cancer, but the number of deaths averted is much smaller than in older women and the number of false-positive tests and unnecessary biopsies are larger.

·      Women with a parent, sibling, or child with breast cancer may benefit more than average-risk women from beginning screening between the ages of 40 and 49 years.

·      The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women age 75 years and older.

·      The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of tomosynthesis (3-D mammography) as a screening modality for breast cancer.

The ACS and USPSTF guidelines are now more consistent and state that the decision to start screening mammography prior to age 50 years should be an individual one. Both guidelines agree that for average-risk women younger than 45 years, the harms from false positive screening mammograms outweigh the benefits. For women older than 55 years, biennial mammography is likely to provide the most benefits while limiting the harms. The new ACS recommendation to stop screening for older women with life expectancies of less than 10 years is consistent with the emphasis on functional versus chronologic age.  ACS is also recommending ending physical for screening purposes by doctors entirely.

These recommendations do not apply to women age 40 years and older who are at high risk because pre-existing breast cancer or a previously diagnosed high-risk breast lesion and who are known to have underlying genetic mutation (such as a BRCA mutation or other familial breast cancer syndrome) or a history of chest radiation at a young age.  Women at high risk for developing breast cancer will require a more personalized screening than the vast majority of women who are at average risk.

There will be many professional societies and well meaning doctors who will disagree with the new guidelines from ACS and USPSTF but until and when a well designed prospective randomized study provides findings that differ with the above mentioned recommendations they will likely stand.

Mediterranean Diet may Reduce Breast Cancer Risk - The PREDIMED Trial

 

A paper by Toledo et al published in JAMAInternal Medicine suggests that women could reduce their breast cancer risk by following a version of the Mediterranean diet that goes heavy on extra virgin olive oil.

The study was conducted within the frame of PREDIMED trial a 1:1:1 randomized, single-blind, controlled field trial from 2003 to 2009, on 4282 women aged 60 to 80 years who were at high cardiovascular disease risk.

Participants were randomly allocated to a Mediterranean diet (MeDiet) that was supplemented with extra-virgin olive oil (EVOO), a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat).

After a median follow-up of 4.8 years, they identified 35 confirmed cases of breast cancer.  The observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios versus the control group were 0.32 (95% CI, 0.13-0.79) for the Mediterranean diet with extra-virgin olive oil group and 0.59 (95% CI, 0.26-1.35) for the Mediterranean diet with nuts group. When both MeDiet groups were merged together, they observed a 51% relative risk reduction (95% CI, 0.25-0.94). When they excluded women who were diagnosed with breast cancer during the first year after enrollment, the results remained unchanged.  The information that was collected in this study was on invasive breast cancers only therefore noninvasive tumors such as DCIS, in situ cancers, were not included or analyzed in this trial.

The data from the PREDIMED trial, suggest a significant inverse association between consumption of a MeDiet supplemented with EVOO and breast cancer incidence. A high consumption of EVOO (≥15% of total energy intake) seems to be instrumental in obtaining this significant protection. A non-significant risk reduction was observed with the MeDiet supplemented with nuts.

In a different trial, the Lyon Diet Heart Study, which was also a randomized trial, a protective effect of a Mediterranean-type diet against overall cancer incidence was observed, supporting the hypothesis of an anticancer effect of the MeDiet.

The low rate of breast cancer among women in the PREDIMED trial should not be surprising. If the MeDiet is actually protective against breast cancer, a low incidence is to be expected in a study with these characteristics, especially when overall adherence to such diet was good already at baseline. 

Several biological mechanisms could explain the anti-carcinogenic properties of EVOO. All types of olive oil provide a high supply of monounsaturated fatty acids, mainly oleic acid, as well as squalene, but EVOO also contains additional biologically active compounds as polyphenols.

These compounds are known to have a likely role in breast cancer prevention due to inhibition of tumor growth and proliferation, migration, and invasiveness of breast cancer cells in both in vitro or in vivo breast cancer models.  Olive oil has been associated with increased apoptosis of cultured breast cancer cells. It has also been reported to reduce intracellular reactive oxygen processes and to prevent oxidative DNA damage in both human breast epithelial cells and human breast cancer cells.

The authors conclude that the findings of their trial suggest a beneficial effect of the Mediterranean diet supplemented with extra-virgin olive oil as a primary prevention of breast cancer.  The authors also state that their findings need to be confirmed with longer-term and larger studies, as breast cancer in addition to being the most prevalent cancer in women worldwide, with 1.7 million new cases diagnosed in 2012 while its incidence is has increased by 20% due to growth and aging of the population.

JAMA Intern Med. published online September 14, 2015.