Cancer screening refers to the use of tests to detect cancer in individuals who do not have any symptoms of the disease. In general, the primary goal of screening is to reduce cancer deaths by detecting cancer at an earlier and more treatable stage. For some types of cancer—including cervical cancer—screening can also play a role in cancer prevention. Screening for cervical cancer can identify precancerous changes to the cervix. Treatment of these precancers can then prevent the development of invasive cancer.

The Pap test is a screening test that has had a tremendous impact on cervical cancer incidence and mortality. During a Pap test, a sample of cells is removed from the cervix and evaluated under a microscope. If the cells appear abnormal, additional testing is often recommended.

More recently, tests for high-risk types of human papillomavirus (HPV) have also been incorporated into cervical cancer screening programs. Persistent HPV infection causes most cases of cervical cancer.

Decisions about how frequently screening tests should be performed can be quite complex. Although frequent testing may seem like a good thing, testing too frequently can increase the risks of screening without improving cancer outcomes. The most recent recommendations from the USPSTF are based on an updated review of the available research on cervical cancer screening. The primary recommendations are as follows:

• For women between the ages of 21 and 65 who are screened with a Pap test, testing is recommended every three years.
• Another screening option is the combination of a Pap test and an HPV test. If combination testing is performed, it is recommended every five years for women between the ages of 30 and 65. Routine HPV testing is not recommended for women under the age of 30 because many young women have HPV infections that will clear on their own without causing problems.
• Cervical cancer screening is not recommended for women under the age of 21.
• For women over the age of 65, cervical cancer screening is not recommended for women who have adequate prior screening and are not otherwise at high risk for cervical cancer.

These recommendations are intended for healthy women who do not have a history of cervical abnormalities. Women who have questions about the screening approach that’s best for them are advised to talk with their physician.

Reference: MoyerVAon behalf of the US Preventive Services Task Force. Screening for cervical cancer: US Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. Early online publication March 14, 2012.

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Approximately 20-25% of breast cancers overexpress (make too much of) a protein known as HER2. Fortunately, the development of drugs that specifically target HER2-positive breast cancer has improved outcomes. These drugs include Herceptin, Tykerb, and the investigational drug pertuzumab.

Combinations of HER2-targeted therapies have shown a benefit in studies of women with metastatic breast cancer (cancer that has spread to other parts of the body), and researchers are also evaluating these combinations in women with earlier-stage breast cancer.

The NeoALTTO study is a Phase III clinical trial that enrolled 455 women with early, HER2-positive breast cancer. The study was restricted to women with operable breast cancer greater than 2 cm in size. Study participants were assigned to one of three neoadjuvant (before surgery) treatment groups:

1)    Tykerb plus chemotherapy

2)    Herceptin plus chemotherapy

3)    Herceptin plus Tykerb plus chemotherapy

The primary outcome of the study was the pathological complete response (pCR) rate. A pCR refers to the disappearance of detectable cancer at the time of surgery. After surgery, patients received additional chemotherapy and HER2-targeted therapy.

Response rates were highest among women treated with the combination of Herceptin and Tykerb: a pCR was achieved by 51.3% of women in the combined Herceptin/Tykerb group, 29.5% of women in the Herceptin group, and 24.7% of women in the Tykerb group.

These results suggest that a combination of Herceptin and Tykerb may be more effective than either drug alone. The difference between Herceptin alone and Tykerb alone was not statistically significant in this study (i.e. it could have been due to chance alone), but the results of another study—published in Lancet Oncology—suggest that if only one the drugs is used, Herceptin may be more effective.

References:

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Of the more than one million new diagnoses of skin cancer each year, roughly 68,000 involve melanoma. More than 8,000 people die of melanoma each year in theUnited States. What makes melanoma so dangerous is that it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.

In order to provide more individualized and more effective cancer therapy, much research has been focused on determining specific pathways involved in cancer cell growth or survival. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several types of cancer. Approximately half of all melanomas carry a specific BRAF mutation known as V600E. Zelboraf targets this mutation, and was approved in 2011 for treatment of certain patients with advanced melanoma that carries the V600E mutation.

To further evaluate Zelboraf in the treatment of advanced melanoma, researchers conducted a Phase II clinical trial among 132 patients with previously treated metastatic melanoma. The study was restricted to patients with melanomas that carried the V600E BRAF mutation. All study participants were treated with Zelboraf.

• 53 percent of patients had a response to treatment (a reduction in detectable cancer)
• Median progression-free survival (survival without a worsening of the cancer) was 6.8 months.
• Median overall survival was almost 16 months. This is better than the 6- to 10-month median survival that was seen in the past among patients with metastatic melanoma.
• The most common side effects of treatment were joint pain, rash, sensitivity to light, fatigue, and hair loss.
• Squamous cell skin cancer was diagnosed in 26 percent of patients. Increased rates of squamous cell skin cancer have also been reported in other studies of Zelboraf, and patients should be aware of this risk. Squamous cell skin cancer usually does not spread to other parts of the body and can be treated with surgery.

These results provide additional evidence that Zelboraf improves outcomes among patients with advanced melanoma that carries a V600E BRAF mutation.

Reference: Sosman JA, Kim KB, Schuchter L et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. New England Journal of Medicine. 2012;366:707-714.

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ALL—a fast-growing cancer of the white blood cells—is the most commonly diagnosed type of leukemia in children. Each year, there are approximately 6,000 new cases of ALL diagnosed in theUnited States.

In recent decades, progress made in clinical trials has led to substantial improvements in survival for children diagnosed with ALL. In the 1960s, five-year survival for children with ALL was less than 10 percent. By the late 1980s and early 1990s, this figure had increased to 77 percent.

To explore more-recent trends in ALL outcomes, researchers collected information about more than 21,000 children and adolescents who had participated in clinical trials conducted by the Children’s Oncology Group (COG). The study participants had been diagnosed with ALL between 1990 and 2005, and were between the ages of 0 and 22 years at the time of diagnosis.

The Children’s Oncology Group involves more than 200 institutions in theUnited States,Canada,Australia, andNew Zealand.

• Five-year survival increased from 83.7 percent during 1990-1994 to 90.4 percent during 2000-2005.
• Survival increased for all groups of patients except those under the age of 1 year. Five-year survival in infants remained fairly steady at slightly over 50 percent.

This study highlights the ongoing improvement in outcomes for children and adolescents with ALL. Maintaining high levels of participation in clinical trials will be important for further progress. Areas in which progress is needed include the treatment of infants with ALL.

Reference: Hunger SP, Lu X, Devidas M et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the Children’s Oncology Group. Journal of Clinical Oncology. Early online March 12, 2012.

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Lymphoma refers to cancer that involves the cells of the immune system. Two broad categories of lymphoma are Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Several different subtypes of non-Hodgkin lymphoma have been identified, some of which are slow-growing and some of which are more aggressive. Different types of lymphoma require different approaches to treatment.

Having lymphoma diagnosed during pregnancy is uncommon, and relatively little information has been available about the management and outcome of lymphoma in pregnant women. To explore this issue, researchers collected information about 82 women who had been diagnosed with lymphoma during pregnancy. The women were diagnosed at one of nine largeUSmedical centers between 1998 and 2011.

The median age of the women was 31. Fifteen percent of the women were diagnosed with lymphoma in the first trimester of pregnancy, 46 percent were diagnosed in the second trimester, and 35 percent were diagnosed in the third trimester.

• 48 women (63 percent) started lymphoma treatment during pregnancy. Treatment began no earlier than the second trimester of pregnancy.
• 28 women (37 percent) delayed lymphoma treatment until after delivery. A majority of these women were diagnosed with lymphoma late in the third trimester.
• Six patients terminated the pregnancy and received immediate chemotherapy. Five of these patients were in the first trimester of pregnancy and one was early in the second trimester and required treatment with high-dose methotrexate.
• Of the women who continued pregnancy, the median gestational age at the time of delivery was 37 weeks among those who started treatment during pregnancy and 38 weeks among those who delayed treatment until after delivery.
• Birth weight was similar in the two groups. There was one still-birth and one infant with a major birth defect among the women who received lymphoma treatment during pregnancy.
• Three-year overall survival among the women was 92 percent among those who started treatment during pregnancy, 83 among those who started treatment after delivery, and 100 percent among those who terminated the pregnancy.

Since each woman’s situation is different, decisions about how best to manage lymphoma diagnosed during pregnancy will need to be individualized. The results of this study, however, suggest that many women experience good pregnancy outcomes as well as good lymphoma outcomes.

Reference: Evens AM, Advani RH, Lossos IS et al. Lymphoma in pregnancy: excellent fetal outcomes and maternal survival in a large multicenter analysis. Presented at the 53^rd ASH Annual Meeting and Exposition.San Diego,CA, December 10-13, 2011. Abstract 623.

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Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.

Carfilzomib is a type of targeted drug known as a proteasome inhibitor. It has produced good results in patients with relapsed or refractory multiple myeloma, and is also being evaluated in patients with earlier-stage disease. Carfilzomib is taken orally (by mouth).

To evaluate carfilzomib among patients with newly diagnosed multiple myeloma, researchers conducted a Phase I/II clinical trial among 53 patients. All patients were treated with a combination of carfilzomib, Revlimid, and low-dose dexamethasone.

• 94 percent of patients had at least a partial response (a partial reduction in detectable cancer) after completing the first cycle of treatment.
• Responses continued to improve with additional treatment cycles. Among patients who had received at least 12 cycles of treatment, all had at least a very good partial response.
• After 9.5 months of follow-up, all of the patients were alive and only one had experienced a worsening (progression) of their cancer.

These results suggest that the combination of carfilzomib, Revlimid, and low-dose dexamethasone is active against newly diagnosed multiple myeloma. Carfilzomib will continue to be evaluated among patients with various stages of multiple myeloma.

Reference: Jakubowiak AJ, Dytfeld D, Jagannath S et al. Final results of a frontline Phase 1/2 study of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in multiple myeloma (MM). Presented at the 53^rd ASH Annual Meeting and Exposition.San Diego,CA, December 10-13, 2011. Abstract 631.

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The liver is the largest organ in the body and is responsible for many vital functions. Among other things, the liver removes harmful substances from the blood, contributes to the digestion of food, and stores nutrients and energy.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer (cancer that begins in the liver). Factors that increase the risk of developing HCC include long-term, heavy alcohol use and chronic infection with hepatitis B or C viruses.

Liver cancer is the third leading cause of cancer death worldwide. Historically, rates of HCC have been lower in the United States than in other countries, but the disease is on the rise.

To explore trends in HCC in a single, well-defined population, researchers collected information about liver cancer cases diagnosed in Olmsted County, Minnesota. Information was available about 104 people who had been diagnosed between 1976 and 2008.

• The frequency of new cases increased over time. The number of new cases per 100,000 people per year was 3.5 during 1976-1990, 3.8 during 1991-2000, and 6.9 during 2001-2008.
• Alcohol use was the most common risk factor among cases diagnosed during the earliest two time periods. In the most recent time period (2001-2008), hepatitis C was the most common risk factor, and was found in close to 45 percent of the cases.
• Liver cancer survival also increased over time. Median survival increased from 3 months in the earliest time period to 9 months in the most recent time period.

These results provide additional evidence that the frequency of liver cancer has increased sharply in the US, and that chronic infection with hepatitis C is a major contributor.

Reference: Yang JD, Kim B, Sanderson SO et al. Hepatocellular carcinoma in Olmsted County, Minnesota, 1976-2008. Mayo Clinic Proceedings. 2012;87:9-16.

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Menopause—when menstrual cycles end and ovarian hormone production drops dramatically—produces symptoms such as hot flashes and night sweats in up to 80% of women. When these symptoms are severe, they can have a profound effect on a woman’s quality of life and ability to function.

For many years, hormone therapy with estrogen (with or without progestin) has provided an effective way for women to manage menopausal symptoms. Studies over the last several years, however, have raised some concerns about the health effects of hormone therapy. In the Women’s Health Initiative (WHI) clinical trial of estrogen plus progestin, hormone use decreased the risks of fracture and colorectal cancer, but increased the risks of heart disease, breast cancer, stroke, and blood clots.[1] More recent reports suggest that combined hormone therapy may also increase lung cancer mortality.[2]

Initial reports from the WHI study of estrogen alone found that estrogen alone did not appear to increase the risk of breast or lung cancer, but did increase risk of stroke.[3] Because estrogen alone increases the risk of endometrial (uterine) cancer, it is generally only used in women who have had a hysterectomy.

In 2011, updated results from the study of estrogen alone suggested that estrogen may actually reduce the risk of breast cancer.[4] These results were further explored in the current analysis. Information was available about 7,645 postmenopausal women who had been followed for a median of close to 12 years.[5]

• Compared with women in the placebo group, women in the estrogen group were 23 percent less likely to develop invasive breast cancer. Estrogen was also linked with a reduced risk of dying from breast cancer.
• The reduced risk of breast cancer among estrogen users was only seen in women who were not at increased risk of breast cancer to start with. Among higher-risk women (those who had a history of benign breast disease or a family history of breast cancer), estrogen did not reduce the risk of breast cancer.

These results should be reassuring to women who have had a hysterectomy and choose to use estrogen alone to manage menopausal symptoms: estrogen alone does not appear to increase the risk of breast cancer and may actually decrease risk. This potential benefit of estrogen does not appear to apply to women at increased risk of breast cancer. Furthermore, any potential benefits of estrogen must be weighed against the risks.

Women who are considering using hormone therapy to manage menopausal symptoms are advised to discuss the risks and benefits with their physician.

References:

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DCIS refers to abnormal cells in the lining of a breast duct. It is classified as Stage 0 breast cancer—the earliest possible stage. The condition usually does not produce any symptoms (such as a breast lump), and it was an uncommon diagnosis prior to the introduction of screening mammography. Diagnoses increased greatly once mammography became widespread, and DCIS now accounts for up to one-quarter of all breast cancer diagnoses in the United States.[1]

Treatment of DCIS generally involves either a lumpectomy (removal of the abnormal area of the breast) or a mastectomy (removal of the entire breast). When DCIS is treated with lumpectomy, additional treatment with radiation therapy can reduce the risk of cancer recurrence.

Tamoxifen is a hormonal therapy that interferes with the effects of estrogen. It is commonly used in the treatment of hormone receptor-positive invasive breast cancer, and is also used to reduce the risk of breast cancer in women at high risk of the disease.

The role of tamoxifen among women with DCIS was evaluated in a clinical trial known as NSABP B-24. All women in the study had DCIS that was treated with lumpectomy and radiation therapy. Half the women were given tamoxifen and half were given a placebo. The primary results from the study (published in 1999) indicated that tamoxifen reduced the risk of another breast cancer diagnosis.

In the original study, researchers did not routinely collect or analyze information about the hormone receptor status of the DCIS. The benefits from tamoxifen, however, may vary depending on whether the DCIS was estrogen receptor-positive and/or progesterone receptor-positive.

To explore the relationship between the hormone receptor status of the DCIS and the effects of tamoxifen, researchers analyzed a subset of the women who had participated in the NSABP B-24 study. Information about estrogen receptor status and progesterone receptor status was available for 732 of the original 1,804 study participants.[2] Roughly three-quarters of these women had DCIS that was estrogen receptor-positive.

• Among women with estrogen receptor-positive DCIS, treatment with tamoxifen substantially reduced the likelihood of another breast cancer.
• Among women with estrogen receptor-negative DCIS, the benefits provided by tamoxifen were not statistically significant, suggesting that they could have occurred by chance alone. The relatively small number of women with estrogen receptor-negative DCIS, however, makes it difficult to draw definitive conclusions about the effects of tamoxifen in this group.

These results suggest that adjuvant tamoxifen may benefit women with estrogen receptor-positive DCIS.

References:

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Lung cancer remains the leading cause of death in theUnited States. Each year, more than 87,000 men and 72,000 women die of the disease.

Diesel exhaust is composed of fine particles that can become lodged in the lung. The National Toxicology Program of the US Department of Health and Human Services has classified diesel exhaust as “reasonably anticipated to be a human carcinogen.”

To collect better information about the relationship between exposure to diesel exhaust and health outcomes, researchers from the National Cancer Institute (NCI) and the National Institute for Occupational Safety and Health (NIOSH) conducted the Diesel Exhaust in Miners Study.

The study involved more than 12,000 workers at eight non-metal mining facilities. Non-metal mining facilities were chosen because these types of mines often involve exposure to diesel exhaust from heavy equipment, but usually do not involve high levels of exposure to other causes of lung cancer such as radon, silica, or asbestos. The non-metal substances that were mined for were limestone, potash, salt, and trona.

Measurements of air taken at the mines allowed researchers to develop estimates of diesel exhaust exposure for each job and each year. Information was available for people who worked underground as well as people who worked on the surface.

Two reports were recently published from the study: the first assessed all causes of death among all subjects, and found a higher rate of lung cancer deaths among workers with the highest level of exposure to diesel exhaust.

The second report involved a closer analysis of the lung cancer deaths, and accounted for other lung cancer risk factors such as smoking, employment in other high-risk jobs, and history of respiratory diseases. Key findings from the second report include the following:

• Compared with the workers with the least exposure to diesel exhaust, those who had the highest exposure were roughly three times more likely to die of lung cancer.
• In the subset of workers who were non-smokers, those who had the highest exposure to diesel exhaust were seven times more likely to die of lung cancer.

The most heavily exposed miners had levels of exposure that were well above that of the generalUSpopulation. Lightly exposed underground miners, however, had a level of exposure that is similar to that experienced by people who spend a lifetime in a heavily polluted urban area. This level of exposure was linked with a 50 percent increased risk of lung cancer. The risk from very low levels of exposure to diesel exhaust is uncertain.

The results from these studies provide further evidence that diesel exhaust may increase the risk of lung cancer in humans. Newer diesel engines with lower emissions may reduce the health risks.

References:

National Cancer Institute Press Release. Heavy exposure to diesel exhaust linked to lung cancer death in miners. March 2, 2012.

National Cancer Institute Questions and Answers. Diesel Exhaust in Miners Study: Questions and Answers. March 2, 2012.

Silverman DT, Samaniac CM, Lubin JH, et al. The diesel exhaust in miners study: a nested case-control study of lung cancer and diesel exhaust. J Natl Cancer Inst. March 2, 2012. doi:10.1093/jnci/djs034.

Attfield MD, Schlieff PL, Lubin JH, et al. The diesel exhaust in miners study: a cohort mortality study with emphasis on lung cancer. J Natl Cancer Inst. March 2, 2012. doi:10.1093/jnci/djs035.

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