Participants
From February 2007 to November 2008, 153 subjects were submitted to genetic counseling at the Unit for Hereditary Breast and/or Ovarian Cancer of the "Regina Elena" National Cancer Institute of Rome. The analysis was carried out on a sample of 130 subjects who had cancer of the breast and/or ovaries and/or a family history of tumours (at least one first-degree affected relative). Twenty-one subjects did not complete the questionnaires and psychological tests, two were illiterate.
Genetic counseling procedures
Subjects who requested counseling to the Unit for Hereditary Breast and/or Ovarian Tumours of "Regina Elena" National Cancer Institute of Rome were referred by their physician or came spontaneously under suggestion from relatives, friends, other oncologic patients or mass media information.
The counseling multidisciplinary team included an oncologist/counselor, psychologist, and geneticist. The counseling modalities were designed using a multistep approach as follows:
During the first visit the oncologist/counselor, supported by the psychologist, supplied the patient with information about hereditary cancer syndromes, the mutation of BRCA1/BRCA2 genes, and their involvement in the onset of cancer of the breast and/or ovaries. Further information is supplied regarding transmission, the possibility of prevention and treatment.
Afterwards, the physician asked the patient to sign in an informed consent to collect the family history in order to assess the genetic and cancer risk estimation.
Furthermore, risk estimation and eligibility or non eligibility status for genetic test was also performed following the Modena Criteria [[22, 23], http://www.com.unimo.it/com2000/hbc/alberi/lineeg.htm].
Applying these criteria, subjects were classified as eligible if they were at "high risk", or non eligible if they resulted at "intermediate, or slightly increased risk", as described in Table 1. Only the eligible subjects were proposed to give a blood sample during a second counseling section after 14 days. This lapse of time was chosen to give subjects the time to elaborate the information and to decide with greater awareness.
During the second visit the oncologist/counselor, supported by the psychologist, asked the patient his/her consent for the blood sample.
After six months the subjects knew the genetic test result. During this third visit the physician and the psychologist together communicated the outcome of the test, the possible involvement of the family into genetic counseling and the risk-reducing strategies, they help the subjects to express emotions, doubts, and requests focused on the genetic test outcome and on how to communicate the outcome to the sibling or children [24, 25].
The local Ethic Committee approved the counseling procedures.
At the end of each counseling session the psychologist asked to the patients an informed consent to complete questionnaires and psychological tests.
During the second counseling step, only eligible subjects were proposed to give the blood sample; while for the others or non eligible subjects were organized an "ad hoc" surveillance programmes. This study refers to the data obtained by the questionnaires completed after the first genetic counseling session by 130 subjects. The sample was made up of eligible and non eligible subjects.
Instruments
The questionnaires and psychological tests evaluate the following variables.
Demographic and medical characteristics
Data regarding age, geographic origin, civil status, number of children, education, religion and whether they were religious-practicing or non-practicing, eligibility, pathology, number of relatives affected by cancer of the breast and/or ovaries and the total number of relatives affected by any type of tumour were collected.
Cancer Risk Perception (CRP)
An item adapted from previous research was used to evaluate the perception of the risk of developing a tumour: "Indicate with a cross, on a scale from 0 to 100, that which you think is your current percentage risk of developing a tumour, or redeveloping a tumour of the breast and/or ovaries" [26, 17].
The answer was given on a visual analogue scale from 0 to 100 (100 corresponds to the highest risk). The scale is a ten centimetres line and each millimetre corresponds to one point percent.
Genetic Risk Perception (GRP)
An item adapted from previous research was used to evaluate the perception of the risk of being a carrier of the genetic mutation BRCA1/BRCA2 [10]. "Indicate with a cross, on a scale from 0 to 100, which you think is your current percentage of being a carrier of the genetic mutation which causes cancer of the breast and/or ovaries." The answer was given on a visual analogue scale from 0 to 100% (100 corresponds to the highest risk). The scale is a ten centimetres line and each millimetre corresponds to one point percent.
Objective cancer and genetic risk assessment by BRCAPRO model
Data of the family pedigree were inserted (in a separate moment without the presence of consultant) into the computer programme "Cancer-Gene-Program" (that is based on the BRCAPRO evaluation model) to evaluate the risk of being a carrier of the BRCA1/BRCA2 mutation and the risk to develop breast and/or ovarian tumour[20, 27, 28].
This programme uses Mendelian genetics and the Bayes theory to estimate risk considering the following factors: the number of relatives affected and not affected by a tumour of the breast and/or the ovaries, age at onset, number of generations affected, tumour of the breast in men. The final estimation results are two percent values, one for the risk of being a carrier mutation and one for the risk to develop a tumour. This model has been used on large samples and in many countries. It considers factors which other models omit, and its validity and sensibility (by identifying subjects with probable genetic mutation) has been demonstrated in six centres of genetic consulting [19, 29, 30]. This software is easily available via the internet and it is also user-friendly. The last version is CaGene5, available from the official web site: http://www8.utsouthwestern.edu/utsw/cda/dept47834/files/67943.html.
Accuracy of the perception of risk
The percentage risk of developing a tumour and of being a carrier of a genetic mutation evaluated by BRCAPRO were compared to the percentage of perceived risk in order to assess the adequacy of the perceived risk compared to the objective risk (more details in the statistical methods section).
Anxiety and Depression
The Hospital Anxiety and Depression Scale (HADS) [31], Italian version [32] is used in literature to evaluate the psychological distress in a non-psychiatric setting. It is composed of two scales of 14 items, 7 regarding anxiety and 7 regarding depression. The two scores can be calculated separately with three cut-offs: normal anxiety and depression (0-7), borderline anxiety and depression (8-10), disturbance due to anxiety and depression (≥11). By calculating the sum of the two scales, it is possible to identify the presence of disturbance in adaptation(cut-off 13-18), or an episode of heavy depression (cut-off ≥ 19). No psychological distress is evidenced if the sum of the two scores totals <13.
All instruments used were chosen on the basis of the following characteristics: validation, internal reliability and previous use in literature for populations comparable to the one from which the sample for the present study was drawn.
Statistical methods
Descriptive statistics were used to summarize pertinent study information.
The association between variables was tested by the Pearson Chi-Square test.
A paired sample t-test was used to compare the mean values of the subjective perception of risk, with the objective risk, estimated by BRCAPRO.
The percentage risk of developing a tumour and of being a carrier of a genetic mutation evaluated by BRCAPRO were compared to the percentage of perceived risk in order to assess the adequacy of the perceived risk compared to the objective risk. To make this comparison, Bluman et al. in 1999 [33] calculated the quartiles (≤ 25%, 26%-50%, 51%-75%, ≥ 76%) of both the percentage values of objective and subjective risk and after that they make a comparison between the two values. The variable, resulting from this comparison, categorizes the subjects in overestimators, accurate estimators and underestimators.
Differences between groups ("corrected", "under" and "over" estimators) with Kruskal-Wallis non parametric test were analyzed for age, number of relatives affected by cancer and for distress levels.
Concordance between the subjective perception of risk and the objective risk estimated by BRCAPRO was assessed using Cohen's k coefficient of agreement [34]. Landis and Koch proposed categories for judging K values: K less than 0.0 was considered poor, 0.00 to 0,20 was light, 0.21 to 0.40 was fair, 0.41 to 0.60 was moderate, 0.61 to 0.80 was substantial and 0.81 to 1.00 was perfect [35]. Given ratings on a K-level categorical variable, the marginal homogeneity test was used for calculated agreement between two rates summarized by a K × K cross-classification table.
Given the small numbers, statistical analyses cannot be performed to assess the differences between male and female in risk perception. The SPSS (11.0) statistical program was used for the analyses.