Cancer in poorer countries is a significant and growing health concern. Although infectious diseases like HIV/AIDS, tuberculosis, and malaria tend to be more strongly associated with developing countries, cancer is also a considerable cause of mortality. The World Health Organization has estimated that between 2004 and 2030, global cancer deaths will increase from 7.4 million to 11.8 million.

In an effort to address the disparity in cancer care and outcomes the GTF.CCC was convened by the Dana-Farber Cancer Institute, Harvard Global Equity Initiative, Harvard Medical School, and Harvard School of Public Health in 2009. The purpose of this global task force is to “catalyze expansion of cancer care, control, and prevention with strategies that are appropriate to the health systems of low-income and middle-income countries, accessible to patients with low incomes, and integrated into national health insurance systems.” Specifically, this initiative aims to increase drug access as well as increase access and coverage for preventive measures and diagnostic testing. In order to reach the goals of this global call to action, development of strategies for innovative health-care delivery options that may be implemented in developing countries is crucial.

Efforts to improve and sustain cancer screening, prevention, and care in poorer countries are critical and will continue to expand.

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Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family.

Women with a BRCA mutation have a 54% to 86% lifetime risk of developing breast cancer. Risk of ovarian cancer ranges from 36% to 63% among women with a BRCA1 mutation, and from 10% to 27% among women with a BRCA2 mutation.

Options to manage this increased cancer risk include regular cancer screening, chemoprevention (use of medications to reduce risk), or preventive surgery (surgery before cancer is diagnosed).

Preventive surgery may involve removal of the breasts (prophylactic mastectomy) and/or removal of the ovaries and fallopian tubes (prophylactic salpingo-oophorectomy). Because available screening tests do not appear to reduce ovarian cancer mortality, prophylactic salpingo-oophorectomy is often recommended for BRCA1 and BRCA2 carriers who have completed childbearing.

To explore the effectiveness of prophylactic mastectomy and prophylactic salpingo-oophorectomy, researchers collected information about 2,482 women with a BRCA1 or BRCA2 mutation. The study was conducted at 22 centers in Europe and North America.

• During roughly three years of follow-up, there were no breast cancer diagnoses among the 247 women who underwent prophylactic mastectomy. By comparison, among women who did not undergo prophylactic mastectomy, 7% (98 out of 1372) were diagnosed with breast cancer over a similar follow-up period.
• Risk of ovarian cancer was 1%-2% among women who underwent prophylactic salpingo-oophorectomy, compared with 6% among women who did not undergo prophylactic salpingo-oophorectomy.
• Among women with a BRCA1 mutation and no prior breast cancer, risk of breast cancer was 14% among women who underwent prophylactic salpingo-oophorectomy, and 20% among women who did not undergo prophylactic salpingo-oophorectomy.
• Among women with a BRCA2 mutation and no prior breast cancer, risk of breast cancer was 7% among women who underwent prophylactic salpingo-oophorectomy, and 23% among women who did not undergo prophylactic salpingo-oophorectomy.
• Three percent of women who underwent prophylactic salpingo-oophorectomy died of any cause during follow-up, compared with 10% of women who did not undergo prophylactic salpingo-oophorectomy. Prophylactic salpingo-oophorectomy also reduced the likelihood of dying from breast or ovarian cancer.

The results provide additional evidence that prophylactic mastectomy and prophylactic salpingo-oophorectomy reduce the risk of breast and ovarian cancer among women with a BRCA1 or BRCA2 mutation. Prophylactic salpingo-oophorectomy also reduced overall mortality.

The information provided by this study may help women with a BRCA1 or BRCA2 mutation make a more informed decision about prophylactic surgery. Women are advised to talk with their doctor the options available for preventing breast and ovarian cancer or for detecting these cancers at an early stage.

Reference: Domchek SM, Friebel TM, Singer CF et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304:967-975.

Men 50 years of age or older in the United States are often offered prostate-specific antigen (PSA) testing for the early detection of prostate cancer. The test may be offered at a younger age to men at high risk of prostate cancer. The PSA test measures proteins that are produced and shed by the prostate. PSA levels tend to be elevated when prostate cancer is present, but levels can also be elevated in benign (non-cancerous) conditions affecting the prostate. A concern with the use of PSA testing is that it may identify some cancers that do not require treatment. This is sometimes referred to as “overdiagnosis.” Research suggests that some prostate cancers are very slow-growing and will not affect a man’s health during his lifetime. Diagnosis and treatment of these cancers exposes men to the complications of cancer treatment without providing a benefit. Unfortunately, there is no perfect way to predict which prostate cancers require treatment and which do not.

Studies suggest that approximately 9% of prostate cancers may be the result of inherited genetic susceptibility. Approximately 15% of men with prostate cancer have a first-degree male relative (father or brother) with prostate cancer, compared with 8% of the general population. Identification of specific genes involved in hereditary prostate cancer has proved challenging, but research in this area continues.

Researchers recently conducted a study to evaluate whether the risk associated with family history of prostate cancer is partly due to higher rates of diagnostic testing; higher rates of testing could result in detection of cancers that might otherwise have gone undetected.

In this study conducted in Sweden, researchers evaluated prostate cancer incidence and tumor grade for 22,511 brothers of prostate cancer patients.

• The rate of prostate cancer in the brothers of patients was higher than the rate in the general population.
• Brothers of patients were at particularly high risk of early-stage cancers that are typically detected by PSA testing. The risk of being diagnosed with an early-stage cancer was highest during the first year after the patient’s diagnosis.

The researchers concluded that increased diagnostic testing “among men with a family history of prostate cancer appears to contribute to their increased risk of prostate cancer and to lead to detection bias in epidemiological and genetic studies of familial prostate cancer.”

In other words, at least part of the increased risk of prostate cancer among men with a family history of the disease may be explained by the fact that men with a family history are more likely to undergo prostate cancer testing and more likely to have their prostate cancer detected.

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Treatment of advanced non-small cell lung cancer (NSCLC) often involves chemotherapy. Currently available combination chemotherapy regimens can improve the duration of survival as well as quality of life, but researchers continue to search for ways to improve outcomes for patients with this disease.

Tarceva is a targeted therapy that works by blocking a biological pathway referred to as the epidermal growth factor receptor (EGFR) pathway. The EGFR pathway is involved in cell growth and replication. Tarceva may be used for treatment of NSCLC after failure of initial chemotherapy, for NSCLC maintenance therapy, or for treatment of advanced pancreatic cancer.

Sutent is an oral targeted agent that works by inhibiting multiple biologic pathways involved in the growth, replication, and spread of cancer cells. It has been shown to be effective in the treatment of selected patients with kidney cancer or gastrointestinal stromal tumors, and is also being evaluated in the treatment of other types of cancer. Phase II studies have indicated that the combination of Tarceva and Sutent is active in NSCLC.

To evaluate the combination of Sutent and Tarceva for the treatment of patients with advanced NSCLC, researchers conducted a large, double-blind Phase III clinical trial among patients with previously treated advanced NSCLC. Patients were randomized to receive Sutent combined with Tarceva or Tarceva plus a placebo. The combination of Sutent and Tarceva did not improve overall survival but did significantly improve progression-free survival compared with Tarceva and placebo. Patients in this study were reported to experience no new or unexpected treatment side effects.

Detailed results from this study are expected to be presented at the 35th European Society for Medical Oncology (ESMO) conference in October.

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Research suggests that each 10 gram (slightly less than one drink) increase in daily alcohol consumption increases the risk of breast cancer by roughly 7%-10%.[1] [2] This is a fairly modest increase in risk, but breast cancer is a common cancer; even a small increase in risk may translate into many additional cases on a population level.

Several studies have suggested that the relationship between alcohol and breast cancer varies by the hormone receptor status of the breast cancer. Alcohol tends to be more strongly linked with hormone receptor-positive breast cancer than with hormone receptor-negative breast cancer.

Fewer studies have explored whether the relationship between alcohol and breast cancer varies by type of breast cancer (ductal or lobular). Ductal carcinomas account for roughly 70% of invasive breast cancers in the United States, and lobular carcinomas account for 15%-20% of invasive breast cancers.

To assess the relationship between alcohol and type of breast cancer, researchers evaluated information from the Women’s Health Initiative (WHI) Observational Study.[3] Among more than 87,000 postmenopausal women enrolled in the study, 2,944 developed breast cancer during follow-up.

Information about alcohol intake was collected by questionnaire at the time of study enrollment.

• As expected, alcohol intake was more strongly linked with hormone receptor-positive breast cancer than hormone receptor-negative breast cancer. Compared with never drinkers, women who consumed seven or more drinks per week had an almost two-fold increase in risk of hormone receptor-positive breast cancer, but no significant increase in risk of hormone receptor-negative breast cancer.
• When looking at type of breast cancer, alcohol increased the risk of lobular carcinoma but did not appear to significantly increase the risk of ductal carcinoma. The rate of hormone receptor-positive, lobular breast cancer was 5.2 per 10,000 women per year among never drinkers and 8.5 per 10,000 women per year among current drinkers. By comparison, the rate of hormone receptor-positive, ductal carcinoma was 15.2 per 10,000 per year among never drinkers, and 17.9 per 10,000 per year among current drinkers.

An important limitation of the study is that information about alcohol intake was collected only at the time of study enrollment. The analysis did not account for changes in alcohol intake that may have occurred after study enrollment.

The researchers conclude “Although one of the well-known risks of alcohol is an increased risk of breast cancer, this study suggests that alcohol primarily increases risk of lobular and hormone receptor-positive breast cancer.”

References:

[2] Key J, Hodgson S, Omar RZ et al. Meta-analysis of alcohol and breast cancer with consideration of the methodological issues. Cancer Causes & Control. 2006;17:759-70.

[3] Li C, Chlebowski RT, Freiberg M et al. Alcohol consumption and risk of postmenopausal breast cancer by subtype: the Women’s Health Initiative Observational Study. Journal of the National Cancer Institute. Early online publication August 23, 2010.

Colorectal cancer is the second leading cause of cancer death in the United States. The colon is the first 4 to 5 feet of the large intestine, and the rectum is the last several inches.[1]

Rectal cancer tends to be most common in older people, but can affect younger people as well. In order to assess trends in rectal cancer among people under the age of 40, researchers analyzed information from a large U.S. cancer database: the Surveillance, Epidemiology, and End Results (SEER) Program.[2]

Information was collected about 7,661 patients who had been diagnosed with colon, rectal, or rectosigmoid cancer between 1973 and 2005 and before the age of 40.

• Rates of rectal cancer increased 2.6% per year. In contrast, rates of colon cancer did not change significantly during this time period.
• In spite of the increase in rectal cancer, colon cancer remained the more common type of cancer. Incidence of colon cancer during the study period was 1.11 per 100,000 and incidence of rectal cancer was 0.42 per 100,000.
• The increase in rectal cancer appeared to start around 1984. The increase was observed among all races, and among both men and women.

The reasons for this increase remain uncertain. The researchers conclude, “In the current study, we demonstrated that young patients are developing rectal and rectosigmoid cancer an increasing rate. Although these rates are not high enough to warrant a change in current screening guidelines, we suggest strong consideration of the endoscopic evaluation of young patients presenting with rectal bleeding or other common signs or symptoms of rectal or rectosigmoid cancer.”

References:

[2] Meyer JE, Narang T, Schnoll-Sussman FH, Pochapin MB, Christos PJ, Sherr DL. Increasing incidence of rectal cancer in patients aged younger than 40 years. Cancer. Early online publication August 23, 2010.

Lung cancer remains the leading cause of cancer death in the United States. Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers.

Although patients with advanced lung cancer often experience a range of symptoms, palliative care is often not provided until late in the course of disease. Earlier provision of palliative care (which can be integrated with standard cancer treatment) could reduce symptoms and improve quality of life.

To explore the effects of early palliative care, researchers conducted a study among 151 patients with newly diagnosed, metastatic, NSCLC. Patients were assigned to receive either early palliative care integrated with standard cancer care, or standard cancer care alone.

Patients assigned to early palliative care met with a member of the palliative care team at least monthly. Palliative care visits included assessment of physical and psychosocial symptoms, discussion of goals of care, and assistance with treatment decisions.

Outcomes of interest included quality of life, mood, survival, and receipt of aggressive care at the end of life. Aggressive end-of-life care was defined as any of the following: chemotherapy within 14 days before death, no hospice care, or admission to hospice three days or less before death.

• Patients in the early palliative care group reported better quality of life and mood. Depressive symptoms were reported by 16% of patients in the early palliative care group compared with 38% of patients in the standard care group.
• Patients in the early palliative care were less likely to received aggressive end-of-life care. Aggressive end-of-life care was received by 33% of patients in the early palliative care group compared with 54% of patients in the standard care group.
• In spite of the less aggressive end-of-life care, patients in the early palliative care group tended to live longer. Median survival was 11.6 months among patients in the early palliative care group compared with 8.9 months among patients in standard care group.

The results indicate that for patients with advanced lung cancer, early palliative care improves quality of life and mood. Patients in the palliative care group received less aggressive care at the end of life but lived longer.

Reference: Temel JS, Greer JA, Muzikansky A et al. Early palliative care for patients with metastatic non-small-cell lung cancer. New England Journal of Medicine. 2010;363:733-742.

Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin’s lymphoma that begins in the skin. The most common type of CTCL is mycosis fungoides.

Istodax—a histone deacetylase (HDAC) inhibitor—works by slowing the growth of cancer cells. It was approved in 2009 for the treatment of CTCL in patients who had received at least one prior systemic therapy.

The current report provides final results from one of the studies that contributed to the approval of Istodax. The study enrolled 96 patients with Stage IB to IVA CTCL who had received at least one prior systemic therapy. All patients were treated with Istodax on days 1, 8, and 15 of each 28-day cycle.

• 34% of patients had a response to treatment (reduction or elimination of detectable lymphoma). Six patients had a complete response (no detectable lymphoma).
• Among patients with advanced disease, 38% had a response to treatment. Five patients had a complete response.
• The median time to response was two months, and the median duration of response was 15 months.
• 43% of patients experienced an reduction in itching.
• Side effects tended to be mild, and most commonly involved gastrointestinal disturbances and weakness or lack of energy.

These results provide additional evidence that Istodax is active against refractory CTCL, and generally well tolerated by patients.

Reference: Whittaker SJ, Demierre M-F, Kim EJ et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. Journal of Clinical Oncology. Early online publication August 9, 2010.

As women reach menopause and beyond, more than 80% will experience symptoms such as hot flashes, night sweats, sleep disturbance, and vaginal dryness. Estrogen, with or without progestin, is an effective treatment for many of these symptoms. Over the last several years, however, studies have raised important concerns about the health effects of menopausal hormone therapy.

Studies conducted as part of the Women’s Health Initiative (WHI) have evaluated a range of health outcomes among postmenopausal women treated with either estrogen alone or estrogen plus progestin. Use of estrogen plus progestin was linked with an increased risk of heart disease, breast cancer, stroke, and blood clots and a decreased risk of fractures and colorectal cancer. Use of estrogen alone, which is generally reserved for women who have had a hysterectomy, was linked with an increased risk of strokes and a decreased risk of fractures.

Researchers have also evaluated lung cancer risk in these studies. A previous report from the WHI indicated that combined estrogen plus progestin did not increase the likelihood of getting lung cancer, but did increase the risk of dying of lung cancer.[1]

The current report evaluated lung cancer risk among women treated with estrogen alone.[2] Information was available for 10,730 postmenopausal women between the ages of 50 and 79. All had had a hysterectomy. Women received either estrogen alone or a placebo.

Study participants have now been followed for an average of almost eight years.

The risk of getting or dying from lung cancer was similar among women treated with estrogen and women treated with a placebo.

These results suggest that unlike combined estrogen plus progestin, estrogen alone does not affect lung cancer incidence or mortality in postmenopausal women.

References:

[2] Chlebowski RT, Anderson GL, Manson JE et al. Lung cancer among postmenopausal women treated with estrogen alone in the Women’s Health Initiative Randomized Trial. Journal of the National Cancer Institute. Early online publication August 13, 2010.

Hodgkin’s lymphoma is a cancer of the lymph system and is diagnosed by the identification of a characteristic cell under the microscope (the Reed-Sternberg cell). Hodgkin’s lymphoma typically begins in the lymph nodes in one region of the body and then spreads through the lymph system in a predictable manner. It may spread outside the lymph system to other organs such as the lungs, liver, bone, and bone marrow.

Localized Hodgkin’s lymphoma can be treated with chemotherapy, radiation therapy, or the combination of these approaches. These treatments cure many patients, but the long-term side effects of treatment are an ongoing focus of research. The optimal therapy that cures the most patients with the least side effects is still being determined.

To evaluate treatment with fewer chemotherapy cycles and a reduced dose of radiation therapy, researchers conducted a study among 1370 patients with newly diagnosed Hodgkin’s lymphoma and a favorable prognosis. Patients were assigned to one of four treatment groups:

1. Four cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) followed by 30 Gy of radiation therapy
2. Four cycles of ABVD followed by 20 Gy of radiation therapy
3. Two cycles of ABVD followed by 30 Gy of radiation therapy
4. Two cycles of ABVD followed by 20 Gy of radiation therapy

Freedom from treatment failure and overall survival were similar across treatment groups. Patients who received the most chemotherapy and the highest dose of radiation experienced the highest rate of adverse treatment effects.

These results suggest that treatment with fewer cycles of chemotherapy and a reduced dose of radiation therapy may be as effective as, but less toxic than, more intensive treatment. The researchers caution, however, that the long-term effects of these treatments have not been fully assessed.

Reference: Engert A, Plutschow A, Eich HT et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. New England Journal of Medicine. 2010;363:640-52.