Shorts

briefed by Jule Klotter

Bilateral Mastectomy

An increasing number of women with cancer in one breast are choosing to have both breasts surgically removed. Bilateral mastectomy has been associated with reduced cancer incidence in women with BRCA1, BRCA2, or other high-risk gene mutations. For most women, however, bilateral mastectomy has no survival advantage over lumpectomy (removal of the cancerous tissue) and radiation therapy, according to a 2014 California study. The data for the study came from California’s Cancer Registry. The registry includes demographic information, type and stage of cancer, treatment, and outcome for virtually all cancer cases in that state.

The researchers sought to determine the comparative effectiveness of bilateral mastectomy, unilateral mastectomy (removal of affected breast), and lumpectomy plus radiation. They analyzed data from 189,734 women, diagnosed with stage 0–III cancer in one breast between 1998 and 2011. Median follow-up was 89.1 months. Fifty-five percent of the women underwent a lumpectomy to remove cancerous tissue and follow-up radiation therapy. The entire affected breast was removed in 38.8%, and both breasts were removed in 6.2%. The 10-year all-cause mortality rate for lumpectomy-radiation treatment was 16.8% (95% CI, 16.6%–17.1%) compared to 20.1% for unilateral mastectomy (95% CI, 19.9%–20.4%) and 18.8% for bilateral mastectomy (95% CI, 18.6%–19.0%). The higher mortality rate in the unilateral mastectomy group may be partially due to other health problems and more limited access to care, say the authors; most women in the group had lower socioeconomic status and identified as a racial/ethnic minority.

In contrast, the bilateral mastectomy group consisted primarily of non-Hispanic white women less than 40 years old with private insurance. The use of bilateral mastectomy in this age group increased from 3.6% in 1998 to 33% in 2011. Fears about cancer appearing in the second breast may be one reason for removing an unaffected breast. Cosmetic concerns are another. “Some newer breast-reconstruction methods achieve better symmetry when both breasts are reconstructed simultaneously,” according to the researchers.

Although bilateral mastectomy does not provide a survival advantage in the general population, it appears to increase survival in those with inherited mutations in BRCA1 and BRCA2 breast cancer susceptibility genes. Such mutations occur in less than 1% of the general population. About 5% to 10% of all female breast cancers occur in women with these mutations, according to California Cancer Facts & Figures 2014 (www.ccrcal.org/pdf/Reports/ACS_2014.pdf).

A 2013 Dutch study following women with BRCA1/2 mutations (but no actual cancer) found that women who chose prophylactic bilateral mastectomy (n = 212) had a 99% 10-year overall survival rate compared with 96% for the surveillance group (n = 358). Six women in the surveillance group died (4 from breast cancer), compared with 1 in the mastectomy group. Although that woman was never diagnosed with breast cancer, she developed metastases in axillary lymph nodes, bone, and liver 3.5 years after her bilateral mastectomy. No breast cancer appeared during 1379 person-years of observation in the mastectomy group compared to 57 cases during 2037 person-years of observation in the surveillance group. The researchers conclude, “In healthy BRCA1/2 mutation carriers, [prophylactic bilateral mastectomy] when compared with surveillance reduces [breast cancer] risk substantially, while longer follow-up is warranted to confirm survival benefits.”

Conger K. Breast cancer patients with bilateral mastectomy don’t have better survival rates, researchers find [online press release]. Stanford University News. September 2014. http://med.stanford.edu/news/all-news/2014/09/breast-cancer-patients-with-bilateral-mastectomy-dont-have-bette.html. Accessed December 4, 2014.

Heemskerk-Gerritsen, BAM, Menke-Pluijmers MBE, Jager
A, et al. Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis (Advance Access). Ann Oncol. 2013;1–7. Available at http://annonc.oxfordjournals.org/content/early/2013/04/09/annonc.mdt134.full. Accessed December 27, 2014.

Kurian AW, Lichtensztajn DY, Keegan TH, Nelson DO, Clarke CA, Gomez SL. Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011. JAMA. September 3, 2014;312(9):902-14. Available at http://www.ncbi.nlm.nih.gov/pubmed/25182099. Accessed December 27, 2014.

Counting Calories

Restricting food calories to lose weight ignores an important factor: metabolic effects produced by different macronutrients. In their 2014 commentary for Public Health Nutrition, Sean C. Lucan and James J. DiNicolantonio write, “The statement that ‘a calorie is a calorie’ … implies that any two different foods, which have equivalent amounts of potential energy, will produce identical biological effects with regard to body weight/body fatness when consumed.” In reality, the body reacts to proteins, fats, carbohydrates, and alcohol differently. Food composition affects physiological responses that govern satiety, food consumption, and body composition including production of hormones that stimulate or suppress appetite and raise or lower blood sugar.

Calorie-focused advice discourages consumption of high-fat, nutritious foods such as nuts, nut butters, avocados, olives, olive oil, whole dairy, and oily fish. Dietary fat contains about 9 kcal/gram. Protein and carbohydrates each contain about 4 kcal/gram, and alcohol has about 7 kcal/gram. The bias against fat in our calorie-focused society has led to an obsession with low- and nonfat versions of whole foods. In addition, many products marketed as “low-fat” contain higher amounts of refined, easily absorbed carbohydrates. Overconsumption of white rice, refined flour, fruit juices, and other such carbohydrates play havoc with insulin levels, produce food cravings, and may contribute to leptin resistance – producing metabolic abnormalities and increasing hunger. “The problem with trying to ‘eat less’ and ‘move more’ to achieve – and more importantly, maintain – caloric deficit or negative energy balance is that it is practically and biologically implausible,” say the authors. Fatigue and hunger result, leading to compensatory eating and rebound weight gain.

Lucan and DiNicolantonio are concerned that recent proposals to highlight calories on packaged-food labels and to include calorie tables on restaurant menus simply encourage calorie-counting at the expense of food quality. Low-fat baked potato chips have fewer calories than nuts, but chips and other simple carbohydrates contribute to abdominal fat and metabolic dysfunction. In contrast, eating nuts does not promote metabolic dysfunction. Moreover, recent studies indicate that higher-fat diets that attend to food quality (such as the Mediterranean diet) produce and sustain weight loss comparable to calorie-restricted or higher-carbohydrate diets.

Lucan and DiNicolantonio advocate for whole and minimally processed foods that don’t skew metabolism and encourage overeating: “As a guiding principle, the public health community should not be trying to cut calories from available foods, we should be improving the quality of the foods available that provide our calories.”

Lucan SC, DiNicolantonio JJ. How calorie-focused thinking about obesity and related diseases may mislead and harm public health. An alternative. Public Health Nutr. November 2014;1–11. Available at www.researchgate.net. Accessed February 2, 2015.

Chemicals in Feminine-Hygiene Products

Although the US Food and Drug Administration regulates feminine-hygiene products, little research has been performed on the safety of chemicals used in them. Some chemicals damage vaginal and vulva epithelial tissue. Others are carcinogenic or have endocrine-disrupting effects. Fragrance ingredients, parabens in personal lubricants, pesticides, dioxins in cotton used to make tampons and sanitary pads, and even tampon plastic applicators may have negative effects, according to laboratory evidence. Chemical compounds are readily absorbed by vaginal and vulva mucous membranes. Yet menstrual product research has been a low priority in the US, according to science writer Wendee Nicole.

Because of the sensitive, permeable nature of tissue in the genital area, even “generally recognized as safe” chemicals, such as glycerin, can cause problems. Glycerin and related compounds, commonly used in aqueous-based personal lubricants, pull water out of vaginal and rectal epithelial cells through osmosis, causing irritation and destroying cells. Damaged epithelial cells have been linked to changes in vaginal flora and higher incidence of bacterial vaginosis. The cellular damage may also increase a women’s risk of acquiring sexually transmitted diseases such as herpes and human immunodeficiency virus. Silicone-based lubricants have the least effect on cells, according to today’s research.

Tampons are the most commonly used feminine-hygiene product. Tampon-related deaths due to toxic shock syndrome (TSS) made headlines a few decades ago. Synthetic fibers in high-absorbency tampons, sold at that time, created the perfect environment for Staphylococcus aureus, which produced lethal toxins.When three of the four types of synthetics were taken off the market, TSS rates declined. A few cases are still reported each year. Unlike tampons with synthetic fibers, all-cotton tampons have never been linked to TSS. Long-term effects of pesticides in cotton are unknown.

The Robin Danielson Act, a bill first introduced by Congresswoman Carolyn Maloney (D-NY) in 1999, promotes federal research on feminine-hygiene products and the chemicals that they contain. Although the bill has been voted on repeatedly (last in 2011), it has failed to pass. The majority deems it “‘unnecessary and a waste of money.’”

Nicole W. A question for women’s health. Environ Health Perspect. March 2014;12(3):A71–A75. Available at http://ehp.niehs.nih.gov/122-a70. Accessed December 4, 2014.

Dried Plums for Bones

Eating dried plums (prunes) reverses bone loss, according to animal and clinical studies. This fruit slows bone removal (osteoclast activity) and increases bone formation (osteoblast activity) and glutathione activity, according to a 2013 mouse study. Elizabeth Rendina and colleagues fed adult osteopenic ovariectominzed mice with either a control diet or a diet supplemented with dried plum, apple, apricot, or mango for eight weeks. Dried plum was the only tested fruit to prevent tibial bone loss as well as increase whole-body and spine bone mineral density. In addition, the dried-plum group showed increased bone formation in vertebral trabecular bone that “coincided with improved biomechanical properties, including bone strength and stiffness.”

In clinical studies, dried plums have improved bone-related biomarkers and bone density. In a 2011 study led by Shirin Hooshmand, 160 osteopenic postmenopausal women were randomized into two groups. One group included dried plum (100 g/day) in their diet (about 14 half-dollar-size prunes). This amount improved bone-related biomarkers in an earlier study. Because of dried plums’ laxative effect, the women were asked to reach this dosage gradually. Women in the other group ate dried apples (75 g/day), which provided a comparable amount of energy, carbohydrates, fat, and fiber. Women in both groups also took 500 mg of calcium and 400 IU of vitamin D each day. None of the women were on hormone replacement therapy or taking any other medications known to significantly affect bone metabolism.

In the year-long study, several bone markers were measured at baseline and at 3, 6, and 12 months. Data on diet, physical activity, height, and weight were also gathered at those times. The researchers assessed bone density at baseline and at 12 months using dual-energy X-ray absorptiometry. Two bone turnover markers – serum bone-specific alkaline phosphatase (BALP) and osteocalcin (OC) – declined in the dried-plum group. The decline of BALP was significant at 12 months compared to baseline. In the dried-apple group, serum BALP and OC levels increased. Tartrate-resistant acid phosphatase-5b (TRAP5b), a specific marker of bone loss, “decreased significantly in the dried plum group at 3 months and stayed at the same level at the 6- and 12-month time points.” TRAP5b increased nonsignificantly in the dried-apple group. Inflammation, reflected in serum C-reactive protein, also declined in the dried-plum group but not the dried-apple group.

Both groups showed positive changes from baseline in ulna, spine, femoral neck, total hip and whole-body bone mineral density (BMD). Women in the dried-plum group had a significant improvement in ulna and spine BMD, compared to those eating dried apples. (The study design makes it impossible to parse out the effect of calcium and vitamin D. I’d like to see a control using calcium and D only and a group using plums and no Ca-D.)

Dried plums contain several nutrients known to support bone health including magnesium, vitamin K, boron, and potassium. Moreover, polyphenols extracted from the dried plums reduced osteoclastogenesis and boosted osteoblast activity in two published studies, according to Rendina et al.

For those who are wary of dried plums’ laxative effective, it may be helpful to know that a six-month preliminary study indicates that 50 grams/day of dried plum (about 6-7 prunes) may be as beneficial as 100 grams (FASEB Journal;April 2014).

Hooshmand S, Chai SC, Saadat RL, et al. Comparative effects of dried plum and dried apple on bone in postmenopausal women. Br J Nutr. 2011;106:923–930. Available at www.researchgate.net. Accessed February 2, 2015.

Metti D, Ortiz D, Cravinho A, et al. The effectiveness of daily consumption of 50 g dried plum on improving indices of bone turnover in osteopenic postmenopausal women [abstract]. FASEB J. April 2014;28(1) Suppl.1027.5. Available at www.fasebj.org/content/28/1_Supplement/1027.5.short. Accessed January 7, 2015.

Rendina E, Hembree KD, Davis MR et al. Dried plum’s unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model. PLOS One. March 2013;8(3). Available at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0060569. Accessed February 2, 2015.

Hypofractionated Breast Irradiation

American Society for Radiation Oncology practice guidelines and the Choosing Wisely Initiative recommend fewer weeks of radiation treatment after breast-conserving surgery than is typically used for early stage cancers. Conventional whole breast irradiation (WBI) consists of 5 to 7 weeks of daily treatment. Hypofractionated WBI uses fewer, higher-dose treatments usually given over a 3-week period. Hypofractionated WBI increases convenience, reduces treatment burden, and lowers health-care costs while offering similar cancer control to conventional WBI, according to a study by Justin E. Bekelman, MD, and colleagues.

In their 2014 study, Bekelman et al.looked at claims data from 14 commercial health-care plans (2008–2013). Practice guidelines endorse hypofractionated WBI for early-stage breast cancer patients, aged 50 and older, without axillary lymph node involvement or prior chemotherapy. The guidelines permit its use in younger women and in those with axillary lymph node involvement or prior chemotherapy. Although the use of hypofractioned WBI has increased since 2008, only 34.5% of the women aged 50 or older with early-stage cancer (endorsed group) and 21.2% of the permitted cohort received hypofractionated radiation therapy in 2013.

As expected, the shorter treatment produced cost savings. Adjusted mean total health costs in the year after diagnosis for the hypofractionated-endorsed group was $31,641 for those who used conventional WBI and $28,747 for those treated with hypofractionated WBI (difference, $2894; 95% CI, $1610–$4234; p < .001). Adjusted mean total health costs for the hypofractionated-permitted group was $72,860 for women treated with conventional WBI and $64,273 for those who had hypofractionated WBI (difference, $8587; 95% CI, $5316–$12,017; p < .001).

Partial breast irradiation with the MammoSite catheter (brachytherapy) is another alternative to conventional WBI. Like hypofractionated treatment, MammoSite brachytherapy requires shorter treatment duration and has low rates of local recurrence. Unlike WBI, MammoSite brachytherapy has a higher risk of palpable masses (noncancerous) and telangiectasias (permanent dilation of superficial capillaries), according to a 2013 study led by Kari M. Rosenkranz.

Bekelman JE, Sylwestrzak G, Barron J, et al. Uptake and costs of hypofractionated vs conventional whole breast irradiation after breast conserving surgery in the United States, 2008-2013. JAMA. December 17, 2014;312(23):2542–2550. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC4271796/pdf/nihms. Accessed December 27, 2014.

Rosenkranz KM, Tsui E, McCabe EB, Gui J, Underhill K, Barth RJ. Increased rates of long-term complications after MammoSite brachytherapy compared with whole breast radiation therapy. J Am Coll Surg. Septermber 2013;217(3). Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3808115/pdf/nihms. Accessed December 27, 2014.

Neonatal Gut Microbiota

The establishment of an infant’s gut microbiome rests on a number of prenatal and postnatal factors, according to a 2014 Canadian review article. A diverse microbiome aids immune system development, protects against pathogens, and helps digest food. Some gut bacteria profiles have been linked to immune-related illnesses such as asthma, allergic disorders (e.g., atopic dermatitis, rhinitis), and chronic immune-mediated inflammatory diseases.

Contrary to expectation, babies are exposed to beneficial gut bacteria in the womb, according to recent evidence. DNA from Lactobacillus and Bifidobacterium, both of which are normal residents of a healthy gut, has been detected in placentas. Bifidobacteria have also been found in meconium, amniotic fluid, fetal membranes, and umbilical cord blood taken from healthy mothers and infants.

Factors that change the mother’s microbiota during pregnancy affect a baby’s commensal bacteria composition after birth. A woman’s use of antibiotics around the time of birth (perinatal period) corresponded to delayed colonization by Bifidobacteria and Lactobacillus species in the baby (Faa G et al. J Matern Fetal Neonatal Med 2013;26[52]:35–43). Bifidobacteria and Lactobacillus counts were also lower in infant monkeys whose mothers were stressed during pregnancy. Reduced levels of Bifidobacteria and Lactobacillus correlate to higher risk of allergic conditions, irritable bowel, and inflammatory bowel disease.

The birth process itself is a major factor in the establishment of an infant’s microbiome. The reviewers say, “A number of studies have described altered fecal or intestinal microbiota profiles in cesarean section-delivered infants beginning at 1 day after birth and persisting to 6 weeks, 6 months, and even 7 years of age.” Vaginally born infants typically have more microbial diversity in their GI tract and a higher incidence of Lactobacillus, Prevotella, and Sneathia – all of which are normal inhabitants of a woman’s vagina. Cesarean-delivered babies have high levels of skin microbes, less Bifidobacteria, and less microbial diversity. These microbiome alterations may contribute to Cesarean-delivered children’s higher incidence of immunological disorders. Children born by C-section have a 20% higher risk of asthma, a 10% greater risk of developing juvenile rheumatoid arthritis, and about 40% greater risk of developing other immune defects, according to a 2014 Pediatrics study. These conclusions were based on data from 2 million Danish children born between 1973 and 2012.

A baby’s diet also influences gut microbiota. Commensal bacteria thrive in breast-fed infants. Breast-fed infants had more than twice the number of Bifidobacterium cells in their stool, compared to formula-fed babies in a 2011 study. Other studies report that C. difficile, a GI pathogen, is more prevalent in formula-fed infants.

Investigation into the microbiome’s role in human health is just beginning. “Whether the altered microbiome causes the disease or is the disease affecting the microbiome remains an issue of debate,” write the Canadian reviewers. “ … future research should incorporate extended microbiota analyses, detailed nutrition assessments, and longitudinal measures of disease conditions throughout childhood.”

Bezirtzoglou E, Tsiotsias A, Welling GW. Microbiota profile in feces of breast- and formula-fed newborns by using fluorescence in situ hybridization (FISH) [abstract]. Anaerobe. December 2011; 17(6):478–482. Available at http://www.sciencedirect.com/science/article/pii/S1075996411000333. Accessed February 2, 2015.

Munyaka PM, Khafipour E, Shia J-E. External influence of early childhood establishment of gut microbiota and subsequent health implications. Front Pediatr. October 2014;2:Article 109. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC4190989/pdf/fped-02-00109.pdf. Accessed January 16, 2015.

Ringgaard A. Giant study links C-sections with chronic disorders [online article]. ScienceNordic. December 9, 2014. http://sciencenordic.com/giant-study-links-c-sections-chronic-disorders. Accessed January 10, 2015.

Sevelsted A, Stokholm J, Bønnelykke K, Bisgaard H. Cesarean section and chronic immune disorders [abstract]. Pediatrics. January 1, 2015;135(1):e92–e98. Available at http://pediatrics.aappublications.org/content/135/1/e92.abstract. Accessed January 16, 2015.