Disturbing Déjà vu: When Cancer Comes Back

Guido R. Zanni, PhD
Published Online: Saturday, August 15, 2009

Woman with cancer ribbonsIn the 1930s, 25% of people diagnosed with cancer were cured--defined as living cancer-free forat least 5 years. Today, 66% of people diagnosed with cancer will live at least 5 years, and the 10-year survival rates are approximately 59% in adults and 75% in children.1

Cancer therapy can produce late effects, defined as physical or psychological complications that may not become apparent until years after diagnosis and treatment of the primary cancer. Examples include cardiac problems subsequent to doxorubicin or trastuzumab, clotting disorders from drug treatment or the cancer itself, and skin inelasticity after radiation.

When a cancer survivor develops a cancer unrelated to the original cancer, it is referred to as a new primary malignancy. One of every 6 to 7 cancer patients will develop a new malignancy in his or her lifetime. The overall risk is 14% greater than that in the general population.2 More than 80% of these tumors develop in a separate, independent organ system. Breast cancer (in women), colon cancer, lung cancer, and melanoma account for most cases.1

The risk of developing a new malignancy varies markedly by the patient's age at the first diagnosis (Table). Patients who are first diagnosed in childhood have a 6-fold greater risk of developing a malignancy unrelated to the first (ie, not the primary cancer's recurrence or metastasis).3,4 Patients first diagnosed at approximately age 70 years or older have equal risk to that of the general population.

Historically, researchers postulated that most of these secondary cancers, regardless of the patient's age, were manifestations of genetic susceptibility and/or late complications of drug treatment or radiation. Treating the first cancer allows the patient to live long enough to get a second cancer, which is both troublesome and ironic. Findings from examinations of patients who have multiple primary cancers help us determine what goes awry genetically. Chemotherapy and radiation given to treat a first cancer can be the cause of the second cancer (eg, radiation is closely tied to subsequent sarcoma). Therapy is not a major cause, however, of new malignancies among adult survivors. Smoking or tobacco use and/or alcohol consumption account for approximately 35% of second primary cancers in cancer survivors.2

Poor Lifestyle Choices: Tobacco and AlcoholCancers Related to Smoking chart
Patterns of multiple cancers often reflect the same risk factors that caused the first cancer, and tobacco use is the main culprit. Rates of smoking among cancer survivors are similar to or exceed the rates among the general population.5,6 Tobacco smoking is carcinogenic and can cause or contribute to many cancers. An analysis of the National Health Interview Survey found that 20% to 23% of cancer survivors reported being current smokers.7 Cancer victims who quit smoking often have strong addictions, and recidivism is very high.

Alcohol intake also is a major cause of cancer in the general population and among cancer survivors. Excessive
alcohol intake has been definitively associated with cancers of the oral cavity, pharynx, esophagus, colon, rectum,
liver, larynx, and breast. Its relationship with other cancers is frequently suspected.8 Survivors of prostate, lung,
larynx, and pharynx cancers are more likely to report moderate-to-heavy alcohol use, as are older patients.7

Lifestyle Challenge: Exercise
Only 25% of cancer survivors meet current recommendations for physical activity.7 This is particularly distressing,
because many cancer survivors are at increased risk for treatment-related chronic medical conditions, and inactivity
exacerbates risk.9-11 The Agency for Healthcare Research and Quality's research indicates that physical activity can improve cancer survivors' physiologic and psychosocial health, improve cardiac and respiratory fitness, reduce
fatigue, and elevate quality of life.12

Delayed Treatment Effects
Delayed treatment effects are a significant concern among children. Children and adolescents are especially sensitive to late carcinogenic effects of radiation and chemotherapy.4,13 Solid tumors, having long latency periods, tend to occur ≥5 years after the primary diagnosis. The risk of solid tumors is heightened in the radiation field used to treat the primary cancer; therefore, young patients treated for Hodgkin's lymphoma are at increased risk of breast, lung, and other tumors in the radiated body area.2

Although lifestyle plays a predominant role in second malignancies among adults, delayed treatment effects are the clear cause of some specific second malignancies. Breast cancer survivors who received radiation are at increased risk for lung and esophageal cancers and sarcoma. Patients who are irradiated for cervical and pelvic
cancers are more likely to develop leukemia. Hormonal therapies, especially with tamoxifen, appear to increase the incidence of uterine cancer, although they decrease the incidence of contralateral breast cancer.2 Cancer researchers are constantly working to improve or modify radiation and chemotherapy to lessen the likelihood of second cancers.

Implications for PharmacistsRisk of Secondary Malignancy chart
Although counseling to reduce high-risk behaviors is important for all patients, it is imperative for cancer survivors.
Cancer survivors may be among the most addicted of smokers and drinkers. Pharmacists need a range of interventions, with the ideal goal being cessation of the risky behavior. Should that fail, risk reduction (decreasing the amount and/or number of days of risky behavior) is a reasonable goal. Cancer survivors also need to be aware of and avoid other risk factors, including poor diet, environmental toxins, and excessive
sun exposure.2

Many cancer survivors look forward to returning to normal after they are considered cured; however, cancer will
continue to influence their health status. Long-term surveillance is necessary, and pharmacists should remind cancer survivors to remain vigilant and adhere to screening recommendations. Cancer survivors, because of their complex medical histories, should have copies of their medical records available when they seek health care; their oncologist's or radiation therapist's succinct summary of their condition, treatment, potential complications, and prognosis is invaluable to other clinicians.

When cancer survivors develop a secondary cancer, the conundrum is that the treatment may have caused the cancer, but more treatment is needed to treat the new tumor. Because of this, highly individualized treatment plans are needed. The patient's history is the most important factor in choosing a therapy.2,13

Although some second malignancies are genetically programmed, many are not. Lessening the occurrence of second malignancies, at this point in time, is probably best addressed by concentrating on health behaviors after the diagnosis and minimizing the risk factors and their sequelae. Smoking cessation, reducing alcohol intake, increasing levels of physical activity, avoiding known carcinogens, and complying with suggested cancer screening are recommended approaches.

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