Pinheiro SP, Schernhammer ES, Tworoger SS, Michels KB. Cancer Res 2006:66:5521-5525.

Mounting evidence suggests habitual sleep duration is associated with various health outcomes; both short and long sleep duration have been implicated in increased risk of cardiovascular disease, diabetes, and all-cause mortality. However, data on the relation between sleep duration and cancer risk are sparse and inconclusive. A link between low levels of melatonin, a hormone closely related to sleep, and increased risk of breast cancer has recently been suggested but it is unclear whether duration of sleep may affect breast cancer risk. We explored the association between habitual sleep duration reported in 1986 and subsequent risk of breast cancer in the Nurses' Health Study using Cox proportional hazards models. During 16 years of follow-up, 4,223 incident cases of breast cancer occurred among 77,418 women in this cohort. Compared with women sleeping 7 hours, covariate-adjusted hazard ratios and 95% confidence intervals for those sleeping < or ="5,"> or =9 hours were 0.93 (0.79-1.09), 0.98 (0.91-1.06), 1.05 (0.971.13), and 0.95 (0.82-1.11), respectively. A moderate trend in risk increase towards longer sleep duration was observed when analyses were restricted to participants who reported same sleep duration in 1986 and 2000 (P(trend) = 0.05). In this prospective study, we found no convincing evidence for an association between sleep duration and the incidence of breast cancer.

You may not have heard of pterostilbene (pronounced "tero-STILL-bean") yet. But this berry compound's prospects for inhibiting breast cancer, diabetes, and LDL cholesterol in humans may soon make it as well known as other health-enhancing natural substances.

Standing to reap benefits from pterostilbene's renown are producers of blueberries and grapes, two fruits known to contain this compound.

"The more we study pterostilbene, the more we see its huge potential in the human health field," says chemist Agnes Rimando of ARS's Natural Products Utilization Research Laboratory in Oxford, Mississippi. Her animal studies on the compound have led to several groundbreaking discoveries.

Pterostilbene is one of many aromatic hydrocarbons called "stilbenes." It's a derivative of resveratrol, a compound found in large quantities in the skins of red grapes. Resveratrol burst on the health scene more than a decade ago, when it was found to have cardiovascular and cancer-fighting benefits.

Studies at the time examined resveratrol's role in an apparent phenomenon in which people in France live long lives despite diets very high in saturated fat and cholesterol. It has been theorized, though not yet proven, that red wine's prevalence in the French diet lowers incidence of cardiovascular disease.

Originally isolated from red sandalwood (Pterocarpus santalinus), pterostilbene had already been touted for its fungicidal and antidiabetic properties--and showed potential for lowering blood glucose--when Rimando started experimenting with it in the early 1990s.

"Actually, I isolated pterostilbene from a plant from Thailand back when I was a graduate student at the University of Illinois at Chicago (UIC)," says Rimando. "At that time, I found it to be toxic to a few cancer cell lines, especially breast cancer cells. Later, I had a renewed interest in whether pterostilbene might inhibit cancer when resveratrol was reported to have cancer-preventive activity."

Through experiments using mice, rats, and hamsters, Rimando and collaborators have since helped add chapters to what's known about pterostilbene and what it can do.

Major Findings

Rimando and UIC collaborators made a huge discovery in 2002, when--in tests using rat mammary glands--they found that pterostilbene possessed cancer-fighting properties at similar effective concentrations as resveratrol. Also in that study, Rimando, Oxford plant physiologist Stephen Duke, and scientists at the University of Buenos Aires in Argentina found that pterostilbene is a powerful antioxidant.

Then, in 2004, Rimando solidified pterostilbene's standing with two major announcements to the American Chemical Society. First was the finding--with colleagues in Agriculture and AgriFood in Canada, Oregon Freeze Dry Inc., and North Carolina State and Idaho State universities--that pterostilbene had been detected for the first time in some berries of Vaccinium, a genus of shrubs that includes many types of berries. The research revealed that blueberries are a ready source of the compound. Pterostilbene was already known to exist in very small amounts in red-skinned grapes.

Heartening Results

Then, Rimando announced that pterostilbene can help lower cholesterol and prevent heart disease.

This conclusion was the result of animal studies Rimando did with colleagues at the University of Mississippi and with chemist Wallace H. Yokoyama of ARS's Processed Foods Research Unit in Albany, California.

They found that pterostilbene was similar in activity to ciprofibrate, a commercial drug that lowers LDL cholesterol and triglycerides. "But ciprofibrate can have side effects such as muscle pain and nausea," says Rimando. "Pterostilbene targets the same specific receptor as ciprofibrate, but it's likely to have fewer side effects."

The focus of this work was to determine the ability of pterostilbene and related compounds to activate the peroxisome proliferator activated receptor alpha, or PPARa, a protein in the cell nucleus associated with metabolism that modulates blood lipid levels.

Triglycerides, the chemical form in which fats occur in plants and animals, are a combination of three fatty acids with glycerol. As with cholesterol, elevated levels of triglycerides in the blood have been linked to cardiovascular diseases. Rimando and her colleagues found that the triglyceride-lowering ability of pterostilbene rivals that of ciprofibrate.

The announcements generated a wave of attention for pterostilbene, not only in the United States but in other countries as well. At least two news organizations in Great Britain directly attributed a boom in British blueberry sales to Rimando's findings. And the Oxford lab's results have since been cited by companies marketing products ranging from blueberry extract to juice concentrate to commercially available pterostilbene itself.

Exposure to the synthetic estrogen diethylstilbestrol (DES) given to women during the 1940s to 1960s to prevent miscarriage and morning sickness increases their risk of breast cancer. But what of the risk to the one to two million daughters born to these women? To determine this, scientists followed 2,000 unexposed and 4,800 exposed daughters for 22 to 24 years, querying them periodically about cancer occurrence and mammogram frequency. The authors found the DES daughters had 1.9 times the risk of breast cancer after age 40 compared to unexposed daughters, with increased risk after age 50. They also found that the women who received the highest cumulative dose of DES exposure in utero had the highest breast cancer risk. Of particular concern were the effects that HRT might have on the DES daughters if they opted for HRT to treat menopause symptoms. "Because the commonly used female hormone supplements have been shown to independently increase risk of breast cancer, it might be wise for exposed women to avoid such supplements whenever possible," the authors wrote. Although DES daughters' breast cancer risk is substantially less than their increased risk of vaginal cancer, the authors worried that their breast cancer risk might rise as they age. They noted that DES daughters often fail to have mammograms regularly. The article appeared in Cancer Epidemiology, Biomarkers Prevention.

So-called "DES daughters," born to mothers who used the anti-miscarriage drug diethylstilbestrol (DES) during pregnancy, are at a substantially greater risk of developing breast cancer compared to women who were not exposed to the drug in utero. Reporting in the August issue of the journal Cancer Epidemiology, Biomarkers & Prevention, a nationwide team of researchers found that DES daughters over age 40 had 1.9 times the risk of developing breast cancer, compared to unexposed women of the same age. They also found that the relative risk of developing the cancer was even greater in DES daughters over age 50, but say the number of older women in their study group is, as yet, too small for a firm statistical comparison.

"This is really unwelcome news because so many women worldwide were prenatally exposed to DES, and these women are just now approaching the age at which breast cancer becomes more common," said the study's lead author, Julie Palmer, ScD, professor of epidemiology at the Boston University School of Public Health. She said an estimated one to two million women in the US were exposed to DES, which was frequently prescribed to women from the 1940s through 1960s to prevent miscarriages. The ongoing study suggests that DES-exposed women are developing the typical range of breast cancers after age 40 at a faster rate than non-exposed women of the same ages. The researchers also found that the highest relative risk of developing breast cancer was observed in study participants from the cohorts with the highest cumulative doses of DES exposure. Because of the increased risk observed for DES daughters, the authors urge women who know they were exposed to DES to have regular screening mammograms and to think twice about using supplemental female hormones.

"DES daughters often ask us about use of these hormones," Palmer said. "It might be wise for exposed women to avoid such supplements. Use of hormone supplements is, in itself, an independent breast cancer risk factor, and women may choose not to compound their already increased risk."

When DES, a synthetic estrogen, was developed in 1938, physicians believed that low levels of estrogen in pregnant women led to spontaneous abortions or premature deliveries. In 1953, a clinical trial indicated no benefit with regard to miscarriage prevention. However, use continued in the US until 1971, when researchers determined that DES greatly increased the risk of developing rare cancers of the vagina and cervix in DES daughters; the federal Food and Drug Administration subsequently banned use of the drug in pregnant women. Later research demonstrated that DES increased the risk of breast cancer development in the mothers who used it.

To see if DES daughters and sons were also at greater risk of cancer or other serious illnesses, in 1992, the National Cancer Institute (NCI) funded a long-term study that assembled all known "cohorts," or groups of DES daughters that were already being studied (some since the 1970s), as well as a collection of unexposed women. This particular analysis included 4,817 exposed and 2,073 unexposed daughters, and, to date, 102 cases of invasive breast cancer have occurred in the combined group.

Factoring out other breast cancer risk variables, such as the age when these women first gave birth or their number of children, did not change DES daughters' relative risk of developing breast cancer, Palmer said. She adds that the breast cancer cases "tracked the normal range" of breast cancer subtypes, so are expected to be neither more nor less lethal than is commonly seen. Only a few deaths have occurred in the combined group due to breast cancer, so survival statistics are not yet available, she said. Scientifically, the study may be the first to provide direct evidence that prenatal exposure to excess estrogen may be a risk factor for development of breast cancer, according to Palmer. "That theory has been around, but it has been difficult to study. The DES tragedy offers us a direct way to test the hypothesis," she said.

Although researchers do not know how DES may increase breast cancer risk, Palmer said some scientists believe the excess estrogen increases the number of breast tissue stem cells available at birth--cells which could malignantly transform into cancer. If it's true that excess estrogen in utero impacts breast cancer risk later in life, "there is a concern that other environmental factors that increase fetal exposure to estrogenic compounds may do the same thing," Palmer said. "This study suggests that such environmental exposures may deserve more serious consideration."

Editor's Note: A PDF of the article is available. Please e-mail communications@aacr.org to request a copy.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; healthcare professionals; and cancer survivors and advocates in the United States and more than 60 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis, and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

When Olufunmilayo Olopade, M.D., now 48, was a medical resident in Chicago 13 years ago, she noticed the same disturbing trend among young Black female patients that she'd seen in her native Nigeria: aggressive breast cancer that wouldn't respond to treatment. Olopade watched helplessly as a 35-year-old cousin who had sought treatment in the States succumbed to it. Though research supported what she saw--White women are more likely to get breast cancer, but we tend to get it younger and die from it more frequently--the stats offered little explanation for the disparity. Olopade, a mother of three, became determined to solve the mystery. Today, as director of a cancer-research center at the University of Chicago, she has found an answer that will save lives.

Olopade suspected that the aggressive cancer had a genetic link, so she partnered with Nigerian doctors to study how genes affect the types of cancer that afflict women of African descent. Last spring the team discovered that a genetic mutation often causes tumors to start in different breast cells in Black women than in White women. These tumors are less likely to respond to traditional estrogen-based drugs. "Breast cancer isn't one single disease," Olopade says. "It affects women of different populations in different ways." She's pushing for doctors to rethink how they treat this form of aggressive cancer. And because the prognosis is usually better if cancer is caught early, she's calling for Black women to start screening at younger ages and for those with a family history of the disease to get genetic testing. In September Olopade received the MacArthur Foundation's "genius" award of $500,000 to further her work. "I want to translate research into real help--and better drugs--for women," she says.

The majority of women diagnosed with breast cancer are clinically eligible for two surgical treatment approaches: mastectomy or lumpectomy (also referred to as breast conserving surgery [BCS]). It is well-established that mastectomy and BCS accompanied by radiation therapy confer an equivalent rate of survival for patients without metastatic disease (National Institutes of Health 1990; Fisher et al. 1999). Thus, the surgical treatment of breast cancer is a good example of what has been described as preference-sensitive care, or care situations in which there are two or more treatment options that are medically justified (Wennberg 2002a). As the label implies, when multiple treatment paths are available and clinically appropriate, the decision process should incorporate and be sensitive to patient preferences regarding the various treatment options (Wennberg 2000b).

Several studies have suggested that shared medical decision making between patients and providers can improve patient satisfaction and even improve some clinical outcomes (Kaplan, Greenfield, and Ware 1989; Laine and Davidoff 1996; Deadman et al. 2001). Many clinicians, researchers, and advocates have argued that breast cancer surgery--as a type of preference-sensitive care--provides an excellent opportunity for shared decision making between patient and provider (Guadagnoli and Ward 1998; Gafni, Charles, and Whelan 1998; Fallowfield et al. 1990). A number of interventions promoting shared-decision models in breast cancer surgical treatment have been designed and evaluated (Whelan et al. 1999; Sepucha et al. 2000). In addition, 20 states have passed laws mandating that patients be informed of both mastectomy and BCS as options (Nayfield et al. 1994; Montini 1997).

An explicit assumption in much of this program and policy development is that mastectomy is "over-used" (National Cancer Policy Board 1999; Morris et al. 2000). The observed geographic and sociodemographic variation in rates of mastectomy versus BCS has not only been labeled as a problem in terms of "over-treatment" but also as an explicit indication of a lack of decision involvement or control among breast cancer patients (Lazovich et al. 1991; Wennberg 2002b). As such, increasing the use of BCS is viewed as a positive goal; and the promotion of patient choice and shared decision making is viewed as the primary means by which this goal can be achieved.

Despite a tacit assumption that increasing patient choice will increase the use of BCS, there is some evidence to suggest that increasing patient involvement is not a simplistic goal, and will not necessarily decrease mastectomy rates. The results of several studies emphasize that not all patients are comfortable with or want to participate in medical decision making, even in the case of preference-sensitive care (Pierce 1993; Schneider 1995; Collins, Kerrigan, and Anglade 1999; Robinson and Thompsom 2001). In addition, Keating et al. (2002) found in a sample of early-stage breast cancer patients that only one-half of the patients participated in the decision making process to the extent that they desired, but that those with more active participation had higher rates of mastectomy. Patients' concerns about cancer recurrence, radiation therapy, the personal costs/benefits of breast reconstruction, and other salient aspects of surgical treatment play important roles in the decision process, even in the face of a strong recommendation for BCS from a surgeon (Nold et al. 2000; Katz, Lantz, and Zemencuk 2001; Keating et al. 2002; Katz et al. 2004).

The primary indicator of progress and quality of breast cancer care should not be the rate of BCS alone (Lantz, Zemencuk, and Katz 2002). Rather, a broader context needs to be considered, including important dimensions of patient satisfaction related to both the outcomes and process of care. The purpose of the research presented here was to investigate patterns in and determinants of satisfaction with surgical treatment and the decision making process in a large, population-based sample of women recently diagnosed with breast cancer. Given that breast cancer surgery is a type of "preference-sensitive care," there is no ideal or target rate of BCS (Ganz 1992). Therefore, rather than view the prevalence of BCS as the primary indicator of quality of care, we investigated patient satisfaction along three dimensions: (a) satisfaction with the type of surgery received; (b) satisfaction with the process by which the surgery decision was made; and (c) feelings of ambivalence or regret regarding the type of surgery received. The main objectives were to describe the prevalence of low satisfaction and decision ambivalence/ regret in a population of breast cancer patients, and to identify patient sociodemographic and clinical characteristics--including the type of surgery received--associated with satisfaction and decision appraisal.

A breast cancer scandal broke in the 1990s in the city of Essen, North-Rhine (1), Germany (Koch, 2000). Qualifications of a local pathologist came into question after a review of the clinical histories of 76 patients revealed recurring inconsistencies. Arson in the pathologist's laboratory prevented a retrospective histological review. Based on the pathology reports in clinical records at least 300 females had been diagnosed with breast cancer. In the absence of a second opinion, many of these females had undergone mastectomy.

In 2000 the Allgemeine Ortskrankenkasse (AOK) Rheinland, a large regional German statutory health insurance company, conducted a survey among females with breast cancer to recognize deficiencies of therapy and identify specific patient's needs (Dusseldorf, 2000). Only 71 percent of females felt that they had received sufficient medical information, and only 52 percent had been given information concerning the availability of psychosocial counseling. A year later, in 2001, the Advisory Council for Concerted Action in Health Care (2) at the Federal Ministry of Health and Social Security analyzed health care deficits in chronic diseases affecting large numbers of the population. Data were obtained with specific questionnaires for medical societies, patient support organizations, health insurance companies, and social agencies. A report by the Advisory Council for Converted Action in Health Care demonstrates a dominance of acute medical care and a neglect of prevention and rehabilitation, both indicative of a lack of awareness of the social, psychological, environmental, and biographic references of chronically ill patients.
Lack of a quality-assured program for early detection of cancer (breast screening according to the European guidelines of 1994) (DeWolf and Perry, 1996).

* Inadequate diagnostic procedures (too many mammograms for females under age 50) and inexperienced radiologists (too many operators of mammography equipment see too few cases).

* Too many breast amputations (mastectomy instead of lumpectomy).

* Too many cases with high-dose chemotherapy with or without stem cell support.

* Too often expensive conventionally equipped technical post-operative care instead of symptom-oriented care.

Based on these and the findings for the chronic diseases, the Advisory Council formulated a series of recommendations for treatment of chronically ill patients and outlined requirements for quality assurance, patient contributions, coordination, evidence-based care, prevention, and training and education of patients and care providers. In response, the Federal health authority outlined structured disease management programs under the responsibility of the statutory health insurance companies and regulated the admission to such programs. The risk-structure compensation scheme was modified to assure statutory health insurance companies promoting disease management programs for patients with chronic diseases do not face disadvantages compared to statutory health insurance companies that do not introduce disease management programs. Admission criteria were defined for the disease management programs of diabetes type 2 and breast cancer; followed by those for chronic obstructive lung disease, diabetes type 1, and coronary heart disease. Described here are the design and experiences of the first disease management program for breast cancer

You have breast cancer." At 34, in the prime of my life and my singing career, those were the last words I ever expected to hear from my doctor--especially since there was no history of the disease in my family. I wondered if I was going to die in a day, a week or a year. But I quickly learned that a diagnosis of breast cancer is not a death sentence. Because I had gotten a mammogram, the cancer in my left breast was caught early; after a partial mastectomy and six weeks of radiation, I was declared "cancer-free."

While my body was forever changed, it was my perspective on life that was even more dramatically altered. The doctors said that radiation would make me tired and I thought, Yeah, right. I have so much energy, I figured it would bring me down a notch, to normal. So I continued with my hectic schedule. I shot a video less than a week after the biopsy. I let TV cameras follow me around prior to and right after my surgery to get the message out about breast cancer. I started writing a new album. My attitude was, If I get tired, I'll take a quick break, then I'll get right back to work. It so didn't turn out that way.

A few weeks into treatment, I became a shell of my former self, yet I continued to push on. It was only when I didn't have an ounce of energy left to sing that I got scared. The radiation didn't just take away my voice, it took away my electricity, my power source. I knew I had to step back and stop trying to be everything to everyone. I started to think of radiation as a girlfriend telling me to slow down and take care of myself--and I finally listened.

Slowly but surely, I learned how to bring more balance to my life. I wanted to start investing in the health of my body as well as my mind, and that goal has stayed with me even three years after treatment. I now give myself days off (something I'd never done before). And while it was difficult (my arm atrophied a lot from the treatment), I've started exercising regularly for the first time. I do Bikram yoga; for me it's not about getting a hot bod; it's a way to take time out from my busy life and get in touch with me. My favorite activity of all is hiking in the hills near my home, where the views are beautiful, inspiring and rejuvenating.

Cancer brought out an unexpected femininity in me, too. I had seen myself as a tough chick, dressed in leather, always wearing my signature dark glasses. But now I find myself wanting to be softer, and I'm exploring that side of my personality. I don't care anymore if I have a perfect face--or scars. This is what I look like, and it's okay: I now know that beauty isn't about having perfectly round breasts or a flawless complexion; it's about who I am on the inside, and I have cancer to thank for that insight.

We've all heard the standard advice about battling breast cancer: Limit alcohol intake to no more than one drink a day; exercise most days of the week for 30 minutes a day; schedule your first mammogram at age 40 and every year thereafter--or start ten years earlier than the age of diagnosis for any close relative who had the illness at age 45 or younger. But there's even more you can do to take control of your health and the health of other Black women. Here, more ways to fight the good fight.

NEVER TAKE A "WAIT AND SEE" APPROACH

Breast cancer experts all agree: It's crucial for you to be proactive if you notice a change in your breasts. "If you're told that you have a lump and your doctor says, 'Let's watch it,' ask for more testing," says Marian Johnson-Thompson, Ph.D., director of education and biomedical research development at the National Institute of Environmental Health Sciences. "Say 'I've been reading about breast cancer, and I'm really concerned. I want to make sure it's nothing.' Then urge your M.D. to send you for a mammogram or an MRI."

If you have a loved one who has just been diagnosed, help her navigate the rough road ahead. "When you've been told you have breast cancer, your brain tends to shut down," says Cheryl Kidd, director of education at the Susan G. Komen Breast Cancer Foundation. "You need someone to sit with you, listen to what the doctor is saying, and then help you formulate questions to ask." On the Komen Foundation's Web site (komen.org), you can find more tips to help keep your friend's spirits lifted and malee sure she gets the care she needs.

RECOGNIZE YOUR RISK

Factors you may never have considered--your weight or whether you've ever had a baby, for example--could impact your risk for developing the disease. So while you're on the site, check out the Foundation's risk assessment chart (at komen.org/riskmatrix) to see where you stand. Then talk the numbers over with your doctor--and don't forget to discuss race. Black women under 50 are twice as likely as White women of any age to get more aggressive forms of breast cancer. In addition, while inflammatory breast cancer, a little-known form of the disease that looks more like a rash than a lump, is rare, it disproportionately affects Black women as well and can lead to a rapid demise.

THINK OF YOUR SISTERS

If you've never had breast cancer yourself but have a sister who had or has the illness, researchers want to tall<>

GET TO KNOW YOUR BREASTS

While experts are divided on the benefits of breast self-exams, some women have found cancerous lumps through the process. (And you definitely don't want to miss your doctor's clinical breast exams.) "If you feel something in your breast, regardless of your age, get it evaluated and insist on a follow-up test," suggests Iris C. Gibbs, M.D., assistant professor of radiation oncology at Stanford University Medical Center. It could make all the difference in the world.