Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation.

PURPOSE: Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation. METHODS: We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis. RESULTS: There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07). CONCLUSION: Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.

The risks of cancer in older women with BRCA pathogenic variants: How far have we come?

BACKGROUND: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. METHODS: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow-up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow-up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan-Meier method. RESULTS: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk-reducing mastectomy and bilateral salpingo-oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. CONCLUSION: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately.

Limited family structure and BRCA gene mutation status in single cases of breast cancer.

CONTEXT: An autosomal dominant pattern of hereditary breast cancer may be masked by small family size or transmission through males given sex-limited expression. OBJECTIVE: To determine if BRCA gene mutations are more prevalent among single cases of early onset breast cancer in families with limited vs adequate family structure than would be predicted by currently available probability models. DESIGN, SETTING, AND PARTICIPANTS: A total of 1543 women seen at US high-risk clinics for genetic cancer risk assessment and BRCA gene testing were enrolled in a prospective registry study between April 1997 and February 2007. Three hundred six of these women had breast cancer before age 50 years and no first- or second-degree relatives with breast or ovarian cancers. MAIN OUTCOME MEASURE: The main outcome measure was whether family structure, assessed from multigenerational pedigrees, predicts BRCA gene mutation status. Limited family structure was defined as fewer than 2 first- or second-degree female relatives surviving beyond age 45 years in either lineage. Family structure effect and mutation probability by the Couch, Myriad, and BRCAPRO models were assessed with stepwise multiple logistic regression. Model sensitivity and specificity were determined and receiver operating characteristic curves were generated. RESULTS: Family structure was limited in 153 cases (50%). BRCA gene mutations were detected in 13.7% of participants with limited vs 5.2% with adequate family structure. Family structure was a significant predictor of mutation status (odds ratio, 2.8; 95% confidence interval, 1.19-6.73; P = .02). Although none of the models performed well, receiver operating characteristic analysis indicated that modification of BRCAPRO output by a corrective probability index accounting for family structure was the most accurate BRCA gene mutation status predictor (area under the curve, 0.72; 95% confidence interval, 0.63-0.81; P<.001) for single cases of breast cancer. CONCLUSIONS: Family structure can affect the accuracy of mutation probability models. Genetic testing guidelines may need to be more inclusive for single cases of breast cancer when the family structure is limited and probability models need to be recreated using limited family history as an actual variable.

Management of pain and nausea in outpatient surgery.

The cost associated with surgical procedures has been dramatically decreased by the ability to perform these procedures on an outpatient basis. Pain and nausea, two common symptoms after anesthesia and surgical procedures, are among the greatest concerns for patients and their family members. As a result of the distress and sequelae associated with these symptoms, clinicians have attempted to determine the optimal intraoperative and postoperative symptom management for patients. The purpose of this quality improvement project was to describe the incidence of these symptoms and their management in patients who underwent planned outpatient surgical procedures in a cancer center. A sample of 39 patients were accrued at a comprehensive cancer center over a 3-month period. Data were collected at three specific time points (i.e., preoperatively, at 24 hours and at 7 days postoperatively). Postoperative pain and nausea were generally well managed, but improvement was needed in preoperative patient teaching, including the topics of drug and nondrug interventions. The methods used in this project have potential application for the measurement of other clinical outcomes after outpatient surgical procedures.

Perspectives on the impact of ovarian cancer: women's views of quality of life.

PURPOSE/OBJECTIVES: To describe quality-of-life (QOL) concerns particular to women with ovarian cancer and to examine whether subgroups of patients with ovarian cancer have significantly different QOL concerns. DESIGN: Mailed survey. SAMPLE: Readership of an ovarian cancer newsletter. METHODS: A total of 1,383 surveys were received in response to the survey's inclusion in the November 2002 issue of Conversations! The International Newsletter for Those Fighting Ovarian Cancer, a monthly newsletter circulated to 3,300 women with ovarian cancer (response rate = 42%). Women were asked to complete the 45-item City of Hope QOL Ovarian Cancer Tool (QOL-OVCA) and a short demographic questionnaire. MAIN RESEARCH VARIABLES: Patients' QOL-OVCA scores were compared across six independent variables, including disease status, age at diagnosis, stage at diagnosis, marital status, household income, and use of alternative therapy, controlling for survival time. FINDINGS: Ovarian cancer survivors reported significant QOL concerns across dimensions of physical, psychological, social, and spiritual well-being. CONCLUSIONS: Patients with ovarian cancer experience particular QOL concerns requiring support. Future research is needed to describe the needs of survivors in more diverse populations and to develop and test interventions that can address these QOL concerns. IMPLICATIONS FOR NURSING: Women with ovarian cancer experience QOL concerns common to other patients with cancer and some that are particular to ovarian cancer. Nurses should assess for and aggressively address these QOL concerns.

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers.

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.

Prognostic factors in the surgical management of pericardial effusion in the patient with concurrent malignancy.

BACKGROUND: Pericardial effusion in the patient with cancer presents a unique management problem. Although multiple methods of operative and nonoperative drainage of pericardial effusions have been described, surgical pericardial window remains the standard approach to long-term drainage. Selecting the patient who may benefit from an operative approach presents a difficult challenge. In the present study, we retrospectively analyzed the clinical outcome of 63 consecutive patients with malignancy who underwent surgical pericardial window for symptomatic pericardial effusion between January 1, 1990, and July 1, 2001, at City of Hope National Medical Center in order to try to determine whether the type of cancer, the presence of malignant cells in pericardial fluid, or tissue specimens or the method of surgery influenced the incidence of recurrent pericardial effusion or duration of survival. METHODS: The cohort was comprised of 15 patients with non-small cell lung cancer (NSCLC), 22 patients with breast cancer, 17 patients with hematologic malignancy, and 9 patients with other solid tumors. Pertinent clinical, laboratory, hospital stay, and outcome data including long-term follow-up were recorded. Patients were followed up until the time of last clinical follow-up or death. Univariate survival analyses were performed to determine significant clinical factors contributing to outcome. RESULTS: Median follow-up was 6.6 months for the group and 8.3 months for those alive at last follow-up. Median survival rates for patients with lung, breast, hematologic, and other solid-tumor malignancies were 3.2 months, 8.8 months, 17 months, and 16.4 months, respectively. Preoperative factors that negatively correlated with survival included a diagnosis of NSCLC (p = 0.0014), the presence of a pleural effusion (p = 0.003), or positive pathologic (p = 0.02) or cytologic findings (p = 0.02). CONCLUSIONS: A surgical approach to pericardial drainage is effective (< 5% failure rate) and provides an opportunity for continued therapy with the potential for relief of dyspnea and improvement in quality of life and survival in selected patients.

Microsatellite instability is a rare finding in tumors of patients with both primary renal and rectal neoplasms.

Multiple primary malignancies in an individual patient are thought to be a common feature of hereditary disease. Asymptomatic renal neoplasms have been described in up to 4% of rectal cancer patients. We have assessed whether microsatellite instability is present in the rectal and renal tumors of patients presenting at our institution with primary renal and rectal cancers. Of the seven patients presenting with both diagnoses, paraffin blocks were available from five cases of colorectal cancer and six renal neoplasms. Five of six cases of renal tumors were informative and all were microsatellite instability (MSI) stable. One renal tumor was deemed inconclusive because of inadequate amplification. Four of five cases of rectal cancer were MSI stable. These data suggest that these renal and rectal tumors developed independently of a mismatch repair defect and that, unlike epithelial tumors of the renal collecting system, renal parenchymal lesions are unlikely to be part of the spectrum of hereditary nonpolyposis colorectal cancer.

Effect of genetic cancer risk assessment on surgical decisions at breast cancer diagnosis.

HYPOTHESIS: Breast cancer gene (BRCA) mutation status affects patients' surgical decisions when genetic cancer risk assessment is offered at the time of breast cancer diagnosis, prior to definitive treatment. PATIENTS AND INTERVENTIONS: Outcomes following genetic cancer risk assessment were studied for women newly diagnosed as having breast cancer who were prospectively enrolled in an institutional review board-approved hereditary cancer registry during a 1-year sampling frame. BRCA gene analysis was offered to subjects with a calculated mutation probability of 10% or higher. Review of medical records and telephone survey were used to document surgical treatment decisions following genetic cancer risk assessment. RESULTS: Thirty-seven of 233 women in the registry were enrolled at the time of a breast cancer diagnosis. The interval from diagnosis to genetic cancer risk assessment ranged from 3 to 60 days. The mean calculated probability of a BRCA gene mutation was 21% across the cohort. Two women were not tested because of low prior probabilities of mutation detection, and 3 declined owing to intercurrent psychological stressors. Of the remaining 32 patients, no BRCA gene mutation was detected in 22 (69%), 3 (9%) were found to carry a variant of uncertain significance, and 7 (22%) had a deleterious mutation. All 7 subjects with a deleterious mutation opted for bilateral mastectomy, whereas 20 of 22 patients with negative test results chose stage-appropriate treatment (P<.001). CONCLUSIONS: Genetic cancer risk assessment at the time of breast cancer diagnosis significantly affected women's treatment decisions. Although need and feasibility are demonstrated, the logistics of genetic cancer risk assessment during breast cancer diagnosis prove challenging.

The surgical treatment of cancer: a comparison of resource utilization following procedures performed with a curative and palliative intent.

BACKGROUND: Costs associated with the provision of medical care continue to escalate. Therefore, providers must evaluate the cost-effectiveness and benefit to individual healthcare practices. The authors evaluated the immediate and short-term resource utilization needs of patients undergoing surgical intervention with curative or palliative intent. METHODS: Three hundred two patients undergoing surgery with therapeutic intent were observed from the time of admission for intervention until the time of death or until 6 months from the time of the surgical procedure. Surgeons preoperatively identified each case as either curative or palliative in intent. Demographic information, as well as the nature of all interactions with the cancer center, was recorded. RESULTS: Surgeons identified 58 (19%) procedures as palliative and 244 (81%) as curative in intent. Demographic characteristics between the two groups were similar, although recurrent or metastatic disease was more often present in palliative rather than curative patients (P = 0.0078) and palliative intent patients were more likely to have received previous therapy. During the 6-month period, 4690 encounters occurred with the cancer center. The mean number of encounters per patient in each group was similar, although curative intent patients were more likely to have visits with therapeutic intent including chemotherapy administration (P = 0.01), radiation (P = 0.003), or repeat surgical procedures (P = 0.006). In contrast, palliative patients were more likely to be admitted for management of symptoms (P = 0.0001) and had fewer hospital-free days than did curative patients (P = 0.0069). CONCLUSIONS: The average number of encounters for patients undergoing treatment of disease was not significantly different, suggesting that patients undergoing surgery with palliative intent do not require a greater amount of resources than curative intent patients. The nature of the interactions, however, was different, suggesting that resource needs are different and may need to be anticipated in the assessment of how better quality outcomes can be achieved in the palliative surgery setting.

Psychological well being and quality of life in ovarian cancer survivors.

BACKGROUND: This report offers a unique analysis of the psychological distress associated with ovarian cancer in a review of natural correspondence between ovarian cancer survivors and an ovarian cancer newsletter. METHODS: A review of 21,806 letters, cards, and e-mails reflecting correspondence from January 1994 to December 2000 between ovarian cancer survivors and the founding editor of Conversations!: The International Newsletter for those Fighting Ovarian Cancer was performed using ethnographic qualitative research methods. Statements related to the impact of disease were bracketed and coded within physical, psychological, social, and spiritual domains according to the City of Hope Quality of Life Ovarian Cancer instrument. Statements that reflected psychological well being were then evaluated with respect to the disease trajectory (i.e., diagnosis, treatment, remission, recurrence, and advanced disease/end of life). RESULTS: A total of 1282 communications were identified that pertained to psychological well being. Findings based on major themes derived from the analysis included descriptions of stressors associated with disease status. Significant stressors were identified within all phases of diagnosis, treatment, remission, and recurrence. Women described both positive and negative effects of disease and frequently demonstrated resourcefulness and perseverance by sharing coping mechanisms and survival strategies. CONCLUSIONS: The natural correspondence from women with ovarian cancer provided a rare opportunity to capture the psychological concerns of women throughout all stages of the cancer trajectory. Health care professionals' awareness of the common psychological stressors throughout the ovarian cancer trajectory may allow them to identify more readily the needs for support, leading to improvement in overall quality of life.

Current surgical options in the control of cancer pain.

PURPOSE: Pain syndromes resulting from recurrent or metastatic cancer require careful evaluation to determine the cause of the pain and the appropriate and judicious use of antitumor treatment. The choice of therapy must integrate the type of pain, its function, the overall disease burden of the patient, and psychological aspects of the cancer. As a general rule, opioid analgesics are the mainstay of treatment in patients with cancer-related pain. When pharmacologic pain control is insufficient or is associated with intolerable side effects, the surgical management of pain can be considered. OVERVIEW: In this article, we review the options, indications, and side effects of the interventional and surgical methods available for the treatment of cancer-related pain. CLINICAL IMPLICATIONS: Planning surgical treatment for cancer-related pain after a patient's lack of response to therapy with opioid analgesics requires an understanding of sensory innervation as well as a realistic expectation of survival, anesthetic risk, or possibility of incomplete pain relief. As such, surgical interventions must be tailored to the individual patient. Clinicians should keep in mind the surgical alternatives for the effective control of pain when it becomes apparent that medical therapy is ineffective.