Carey A. Cullinane

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.

Psychological well being and quality of Life in Ovarian Cancer survivors

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.

A prospective evaluation of palliative outcomes for surgery of advanced malignancies.

Background: We prospectively evaluated the effectiveness of major surgery in treating symptoms of advanced malignancies.Methods: Fifty-nine patients were evaluated for major symptoms of intent to treat and were followed up until death or last clinical evaluation. Surgeons identified planned operations before surgery as either curative or palliative and estimated patient survival time. An independent observer assessed symptom relief. A palliative surgery outcome score was determined for each symptomatic patient.Results: Surgeons identified 22 operations (37%) as palliative intent and 37 (63%) as curative intent. The median overall survival time was 14.9 months and did not differ between curative and palliative operations. Surgical morbidity was high but did not differ between palliative (41%) and curative (44%) operations. Thirty-three patients (56%) were symptomatic before surgery, and major symptom resolution was achieved after surgery in 26 (79%) of 33. Good to excellent palliation, defined as a palliative surgery outcome score >70, was achieved in 64% of symptomatic patients.Conclusions: Most symptomatic patients with advanced malignancies undergoing major operations attained good to excellent symptom relief. Outcome measurements other than survival are feasible and can better define the role of surgery in multimodality palliative care. A new outcome measure to evaluate major palliative operations is proposed.

Symptom Concerns of Women with Ovarian Cancer

This study describes the symptom experience of women with ovarian cancer. A body of data consisting of 21,806 letters, cards, and e-mails written by ovarian cancer patients was donated to the City of Hope investigators by the founder and editor of Conversations!: The International Newsletter for Those Fighting Ovarian Cancer. Using ethnographic qualitative research procedures, meaningful comments in the data were bracketed and coded within physical, psychological, social, and spiritual domains according to the City of Hope QOL-Ovarian Cancer instrument. Six hundred seventy-seven (677) comments were identified as pertaining to pre- and post-diagnostic symptomatology. Findings, based on major themes derived from the analysis, included distress over delayed diagnoses given the presence of pre-diagnosis symptoms. Frequently described post-diagnosis symptoms included pain, fatigue, gastrointestinal effects, and menstrual and fertility changes. Women demonstrated resourcefulness and optimism by sharing innovative ideas for coping with varied symptoms. Significant attention was dedicated to complementary and alternative therapies, both for symptom management and with curative intent. Findings demonstrate the need to improve diagnostic tests, symptom management, and patient education.

Patient and surgeon decision making regarding surgery for advanced cancer

PURPOSE/OBJECTIVES To describe a program of research related to outcomes of palliative surgery and focus on one phase of this research involving decision making by patients and surgeons considering surgery for advanced disease. DESIGN Descriptive. SAMPLE 10 patients undergoing surgery and 3 oncology surgeons. METHODS Qualitative interviews were conducted with patients and their surgeons pre- and postoperatively. Transcripts were content analyzed to identify major themes in patient and surgeon interviews based on study questions. MAIN RESEARCH VARIABLES Decision making, palliative surgery, quality of life. FINDINGS The study findings highlight the issues of greatest concern to patients and surgeons considering palliative surgery. This phase was an important component of the overall program of palliative surgery research. CONCLUSIONS Comprehensive care for patients with advanced cancer seeks to achieve a balance of providing aggressive care, ensuring optimum symptom management, and maintaining a focus on comfort. Further study of palliative surgery as an aspect of interdisciplinary care is warranted. IMPLICATIONS FOR NURSING Patients undergoing surgery for advanced disease require expert nursing care to address quality-of-life concerns. Further research is needed in this area.

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

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.

Quality of Life in Patients With Colorectal Metastasis and Intrahepatic Chemotherapy

Background:Liver metastasis from colorectal cancer remains an oncological challenge. Hepatic chemotherapy has been used; however, rigorous quality of life (QOL) measurements are lacking. The aim of this study was to describe unique QOL issues to formulate a specific tool for this population.Methods:A purposive sample was identified of patients treated with intrahepatic chemotherapy. Consenting patients completed a demographic tool and the City of Hope QOL Scale/Cancer Patient survey. An in-depth interview on QOL concerns was conducted, taped, and transcribed verbatim. The data from the interviews were coded to identify recurrent themes.Results:Sixteen patients participated. Physical well-being was maintained. Significantly lower subscale scores were noted for psychological, social, and spiritual domains compared with nonpatient norms (City of Hope volunteers; n = 169). Patients found intrahepatic chemotherapy convenient but were unable to pursue vigorous activity, and their sleep habits changed. Psychologically, patients felt reassured to receive specific therapy to their liver.Conclusions:Pilot evaluation of QOL in this population revealed changes in physical, psychological, social, and spiritual dimensions. Both disease- and treatment-specific concerns were identified, and the results provide evidence for items to include in a QOL questionnaire specific to this population.

Treatment of infertility does not increase the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation

OBJECTIVE To evaluate the relationship between use of fertility medication (i.e., selective estrogen receptor [ER] modulator, gonadotropin, or other) or infertility treatment (i.e., IVF or IUI) and the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation. DESIGN A matched case-control study of 941 pairs of BRCA1 or BRCA2 mutation carriers with and without a diagnosis of ovarian cancer. SETTING Genetic clinics. PATIENT(S) Detailed information regarding treatment of infertility was collected from a routinely administered questionnaire. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals associated with fertility treatment. RESULT(S) There was no significant relationship between the use of any fertility medication or IVF treatment (odds ratio, 0.66; 95% confidence interval 0.18-2.33) and the subsequent risk of ovarian cancer. CONCLUSION(S) Our findings suggest that treatment for infertility does not significantly increase the risk of ovarian cancer among women with a BRCA mutation.

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.

TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome.

The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2, MSH6, MLH1, PMS2 and EPCAM. Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases.