Exercise linked to reduced risk of several cancers

Physical activity has been associated with lower risk of heart disease and all cause mortality, but its association with risk of cancer is not well understood.

Moore et al research published in JAMA Internal Medicine, suggests that exercise is a powerful cancer-preventive and found that physical activity drove down the rates of a broad array of cancers even among smokers, former smokers, the overweight and obese.

Researchers collected data from 12 prospective studies from the United States and Europe and analyzed associations between self-reported physical activities with the incidence of 26 types of cancer in the study period, which lasted 11 years between 1987 and 2004.

A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High versus low levels of physical activity were associated with lower risk of 13 cancers: esophageal adenocarcinoma, liver, lung, kidney, gastric, endometrial, myeloid leukemia, myeloma, colon, head and neck, rectal, bladder, and breast. The data indicated that a higher level of activity was tied to a 7 percent lower risk of developing any type of cancer. Individuals who were very active had a 20% lower risk of cancers of the esophagus, lung, kidney, stomach, endometrium compared with people who were less active.  The reduction was slightly lower for colon, bladder, and breast cancers.

Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma and prostate cancer.  Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers.

Health care professionals should emphasize that physical activity was associated with lower risks of many cancer types and most of these associations were evident regardless of body size or smoking history.

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.

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.