Constance A. Roche

Prevalence of Family History of Breast and Ovarian Cancer in a Single Primary Care Practice Using a Self-Administered Questionnaire

Abstract: Women at high risk of hereditary breast and/or ovarian cancer require specific management strategies for cancer prevention and early detection. The goal of this study was to determine the prevalence of familial breast and ovarian cancer among patients in a primary care practice. Questionnaires were mailed to the 608 women less than 81 years of age in a single primary care practice. Additional mailings and phone calls were used for nonresponders. Data were analyzed by bloodline, the degree of relative, age of diagnosis and cancer type. Women were grouped into three categories of breast/ovarian family history: “no family history,”“insignificant family history,” and “significant potentially high‐risk family history” (women with two or more relatives in a single bloodline with breast and/or ovarian cancer, a single individual with bilateral breast cancer or breast and ovarian cancer, or breast and/or ovarian cancer at less than 40 years of age). A pedigree analysis of women categorized as “significant potentially high‐risk family history” further classified these women as to the likelihood of being at risk for hereditary cancer. Data were obtained from 567 women (93%); 27 patients with a personal diagnosis of breast and/or ovarian cancer were excluded. Of the 540 remaining respondents, 351 (65%) had no family history of cancer, 138 (25.6%) had an insignificant family history, and 51 (9.4%) had a significant family history. Based on pedigree analysis of these 51 patients, 19 were unlikely to be at high risk for hereditary cancer, and 32 (6%) were likely to be at significant risk and warrant intensive evaluation. The large proportion of women identified with a significant family history of breast and/or ovarian cancer has major implications regarding the magnitude of a population‐based process to identify and manage high‐risk individuals. 

Hereditary Breast and Ovarian Cancer and Other Hereditary Syndromes: Using Technology to Identify Carriers

Purpose and MethodsMost patients who harbor a genetic mutation for hereditary breast cancer have not been identified, despite the availability of genetic testing. Developing an effective approach to the identification of high-risk individuals is the key to preventing and/or providing early diagnosis of cancer in this patient population. This educational review addresses these issues.Results and DiscussionUsing data available on the internet, and making assumptions regarding the types and results of genetic testing, we have estimated the number of mutation carriers in the country and the number who have been tested and identified as such. Overall, our ability to fund and more effectively manage carriers is weak. A technological solution is discussed.

The feasibility of using natural language processing to extract clinical information from breast pathology reports.

Objective: The opportunity to integrate clinical decision support systems into clinical practice is limited due to the lack of structured, machine readable data in the current format of the electronic health record. Natural language processing has been designed to convert free text into machine readable data. The aim of the current study was to ascertain the feasibility of using natural language processing to extract clinical information from >76,000 breast pathology reports. Approach and Procedure: Breast pathology reports from three institutions were analyzed using natural language processing software (Clearforest, Waltham, MA) to extract information on a variety of pathologic diagnoses of interest. Data tables were created from the extracted information according to date of surgery, side of surgery, and medical record number. The variety of ways in which each diagnosis could be represented was recorded, as a means of demonstrating the complexity of machine interpretation of free text. Results: There was widespread variation in how pathologists reported common pathologic diagnoses. We report, for example, 124 ways of saying invasive ductal carcinoma and 95 ways of saying invasive lobular carcinoma. There were >4000 ways of saying invasive ductal carcinoma was not present. Natural language processor sensitivity and specificity were 99.1% and 96.5% when compared to expert human coders. Conclusion: We have demonstrated how a large body of free text medical information such as seen in breast pathology reports, can be converted to a machine readable format using natural language processing, and described the inherent complexities of the task.

The Effectiveness of the Gail Model in Estimating Risk for Development of Breast Cancer in Women Under 40 Years of Age

Abstract: Epidemiologic studies have provided information on risk factors for breast cancer. Gail and associates identified five risk factors using the Breast Cancer Detection Demonstration Project (BCDDP) population and developed a model to calculate a composite relative risk (RR). This model is commonly used to counsel women regarding their risk for breast cancer and was used by the National Surgical Adjuvant Breast Project (NSABP) for eligibility for the Breast Cancer Prevention Trial. Because the BCDDP population was composed almost entirely of women 40 years of age or older, our purpose was to evaluate the effectiveness of the Gail model in estimating the risk of breast cancer for women under 40 in the clinical setting. The Gail risk factors were assessed for 124 patients under the age of 40 treated for either ductal carcinoma in situ (DCIS) or invasive breast cancer at the Lahey Hitchcock Medical Center between 1983 and 1995. The RR was calculated using the Gail model. For comparison, two cohorts of women under the age of 40 were used: 107 randomly selected patients who underwent a breast biopsy because of a benign condition and 129 nurses from our institution who responded to a questionnaire that included reproductive and family history information as used in the Gail model. The RR calculated was the RR that existed at the time of the surgical consultation for a suspicious breast lesion. The Tarone‐Ware method was used to analyze statistical significance of differences between distribution. Contingency tables were analyzed using Miettinens modification of Fishers exact test. No differences were found between the median RR for all groups. Only 2 of the 124 patients with breast cancer had a RR of 5 or more (the RR required to enter the Breast Cancer Prevention Trial). The distribution of age at menarche (AGEMEN) was the same for each group. No difference was found for the distribution of age at first live birth (AGEFLB) between those with breast cancer and those with a benign biopsy or the control group. The number of breast biopsies (NBIOPS) was higher in patients with a benign breast biopsy. No difference was found in the distribution of number of first‐degree relatives with breast cancer (NUMREL). Overall the Gail model failed to differentiate those women about to have cancer diagnosed from two control populations. The Gail model is not useful in identifying immediate risk of breast cancer in women under 40 and should not be used for that purpose.

Support needs and acceptability of psychological and peer consultation: attitudes of 108 women who had undergone or were considering prophylactic mastectomy

Objective: Prophylactic mastectomy (PM) offers 90% or greater reduction in risk of breast cancer to women at increased hereditary risk. Nonetheless, acceptance in North America is low (0–27%) and 25–50% of women electing surgery report psychological distress and/or difficulty adapting following PM. Most women also report reduced cancer worry postoperatively. Psychological consultation to aid decision‐making and post‐surgical coping is not routinely offered. This retrospective, cross‐sectional study explored interest in and acceptability of psychological consultation for issues related to PM among 108 women who had undergone or were considering surgery.

Accuracy of Self-Reported Personal History of Cancer in an Outpatient Breast Center

The self-reporting of cancer history is becoming increasingly important, as it frequently guides medical decision-making. We studied the accuracy of personal cancer history using a self-administered questionnaire, comparing the results with the Tumor Registry at our institution. Among 39,662 records, we identified 3614 women with a single cancer in the Tumor Registry who reported none or one cancer on their questionnaire. The sensitivity in self-reporting cancers was 85.7%, ranging from 92.1% for breast cancer to 42.9% for leukemia. The accuracy for breast cancer and Hodgkins Lymphoma was significantly better than other cancers (p=0.00027, CI: 1.4–3.88). Analysis of patients characteristics showed that Caucasians reported breast cancer more accurately than Asian/Pacific Islanders (p=0.008), and those with Jewish ancestry more accurately than non-Jewish (p=0.0435). These results will help us to improve data collection and thus improve medical decision-making.

Breast Cancer Risk and Follow-up Recommendations for Young Women Diagnosed with Atypical Hyperplasia and Lobular Carcinoma In Situ (LCIS).

BackgroundThe risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population.MethodsA retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed. Patient characteristics, pathology and follow-up were determined from chart review.ResultsWe identified 58 young women with atypical breast lesions. Median age at diagnosis was 31 years (range 19–34). 34 patients had ADH, 11 had ALH, 8 had LCIS, and 5 had severe ADH.7 (12%) patients developed breast cancer. The median follow-up was 86 months (range 1–298). Median time to cancer diagnosis was 90 months (range 37–231). 4 cancers were on the same side, 3 were contralateral. 4 were IDC, 1 was ILC, and 2 were DCIS.Cancer was detected by screening mammogram in 4 patients, 2 by clinical exam, and 1 unknown. In the entire cohort, 26 (45%) patients had screening mammograms as part of their follow up, 12 patients had only clinical follow up, and 20 had no additional follow up. 13 patients required subsequent biopsies.ConclusionYoung women with atypical breast lesions are at a markedly increased risk for developing breast cancer and should be followed closely. Based on our findings, we recommend close clinical follow-up, MRI starting at age 25 through age 29, and screening mammograms for those over 30 in this high-risk group of patients.

Chemoprevention acceptance and adherence in women with high-risk breast lesions

Patients with atypical hyperplasia and lobular carcinoma in situ (LCIS) (atypical breast lesions) are at high risk of developing breast cancer, and chemoprevention has been shown to confer a substantial reduction in that risk. Despite this, the overall rate of chemoprevention utilization in this group is low. This study evaluates the efficacy of a formal individualized education and counseling session on patient acceptance and adherence to chemoprevention. Patients with atypical breast lesions having an individualized education and counseling session in a single surgical oncology practice were prospectively entered into a database from 2001 to 2016, and with IRB approval, their data were analyzed. Chemoprevention recommendations, acceptance, duration of treatment, and side effects were recorded. A total of 536 patients were included in this study. Mean age at diagnosis was 52 years (range: 19‐86 years). Chemoprevention was recommended for 386 (72%) of whom 199 (52%) elected to take medication or participate in a chemoprevention clinical trial. At the time of this writing, 72 patients had completed therapy, 69 were still in treatment, and 58 had stopped chemoprevention prematurely. Approximately 55% of the women who accepted chemoprevention in this study will complete 5 years of therapy. A formal individualized education and counseling session can improve chemoprevention acceptance and achieve a reasonable completion rate, thus reducing cancer incidence in women with atypical breast lesions.

A program to increase use of chemoprevention for women with high-risk breast lesions.

46 Background: Tamoxifen, raloxifene, and exemestane have been demonstrated to reduce risk of breast cancer in high-risk women, bututilization is very low.Among the reasons cited are lack of awareness and reluctance of physicians to prescribe. Women with high-risk breast lesions are generally candidates for chemoprevention and can be evaluated and counseled in a high-risk breast clinic. Knowledge about drugs that can prevent breast cancer may increase uptake among high-risk women. METHODS In a single practice, women with a diagnosis of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), or severe atypical ductal hyperplasia/borderline ductal carcinoma in situ are offered an extended visit with a nurse practitioner in the Breast and Ovarian Cancer Risk and Prevention Clinic. The visit includes data collection, patient interview about relevant history and personal preferences, risk assessment, including use of relevant models (via HughesRiskApps.com), and recommendations for surveillance and prevention. Emphasis is placed on understanding of individual risk as well as risks and benefits and appropriateness of chemoprevention and surveillance modalities. Based on personal and family history, women are advised if chemoprevention is appropriate to consider, their choice is made, and they are encouraged to have surveillance in the Breast Clinic. RESULTS Since January 2001, 487 women with a diagnosis of ADH, ALH or LCIS, or severe ADH have been evaluated and counseled in the Breast and Ovarian Cancer Risk and Prevention Clinic. 132/487 (27%) were advised against taking chemoprevention and 355/487 (73%) were appropriate for chemoprevention. Of those for whom chemoprevention was clinically appropriate, 188/355 (53%) took one of the medications, or participated in a chemoprevention trial. 53/188 (28%) did not complete therapy (discontinued at 2 weeks to 54 months) due to preference or side effects. 75 women have completed five years of therapy and 60 are currently on therapy. CONCLUSIONS When provided with personalized information about breast cancer risk and the pros and cons of chemoprevention, many women will choose to take medication to reduce breast cancer risk.

The High-Tech High Risk Clinic

The high risk clinic is an important component of any comprehensive medical system. An effective high risk clinic employs knowledgeable staff, with the ability to assess risk, appropriately counsel, provide, and interpret cancer predisposition genetic testing, and make recommendations and assist individuals to adopt risk reduction strategies. After almost two decades after the cloning of the BRCA genes, and commercial availability and insurance coverage for testing, only a fraction of BRCA mutation carriers have been identified. We address the task of employing twenty first century technology to match the recent advances in genetics and to anticipate implementation of systems to accommodate the large numbers of individuals who will be identified as high risk. Specifically, this chapter will discuss HughesRiskApps (HRA), an integrated, open access software package originated at the Massachusetts General Hospital (MGH) and the Newton Wellesley Hospital (NWH), and that is undergoing continued enhancements through grants, philanthropy and an active user group.