Breast cancer is also a component of the rare Li-Fraumeni syndrome (LFS) in which germline mutations of the TP53 gene on chromosome 17p have been documented. This syndrome is characterized by premenopausal breast cancer in combination with childhood sarcoma, brain tumors, leukemia and lymphoma, lung cancer, colon cancer, and adrenocortical carcinoma [58]. Individuals with LFS often develop multiple primary cancers [59]. A germline mutation in the TP53 gene has been identified in over 50 % of families exhibiting this syndrome, and inheritance is autosomal dominant with a penetrance of at least 50 % by age 50 [60].

One of the more than 50 cancer-related genodermatoses, Cowden syndrome is characterized by an excess of breast cancer, gastrointestinal malignancies, genitourinary malignancies, and thyroid disease (both benign and malignant). Skin manifestations include multiple trichilemmomas, oral fibromas and papillomas, and acral, palmar, and plantar keratoses. Germline mutations in PTEN, a protein tyrosine phosphatase with homology to tensin, located on chromosome 10q23, are responsible for this syndrome. Loss of heterozygosity observed in a high proportion of related cancers suggests that PTEN functions as a tumor suppressor gene. Its defined enzymatic function indicates a role in maintenance of the control of cell proliferation. Disruption of PTEN appears to occur late in tumorigenesis and may act as a regulatory molecule of cytoskeletal function. The lifetime risk of breast cancer in women with PTEN mutations is estimated at 25–50%, with a characteristic early age of onset [61].

Peutz-Jeghers syndrome (PJS) is characterized by gastrointestinal polyposis, particularly hamartomatous polyps, and melanocytic macules on the lips and perioral and buccal tissues [62, 63]. Although the most common cancers in PJS are gastrointestinal, the cumulative risk of breast cancer is 35–54% [63, 64]. Additional cancer risks include pancreatic and ovarian cancers as well as ovarian sex cord tumors with annular tubules (SCTATs) and mucinous tumors of the ovaries and fallopian tubes and Sertoli cell tumors of the testes [65, 66]. Germline mutations in the STK11 gene on chromosome 10p have been identified in the majority of PJS families [63, 67].

Hereditary diffuse gastric cancer (HDGC), which arises from mutations in the CDH1 gene, is associated with an increased risk of lobular breast cancer, with lifetime risks as high as 52 % and an average age of onset of 53 years old [68]. HDGC is unique in the predominant lobular pathology of the breast cancer occurrences as well as the diffuse nature of the gastric cancer cases. The risk for diffuse gastric cancer is >80 % in CDH1 gene carriers [69]. Loss of the E-cadherin protein causes the tumor cells to infiltrate the mucosa of the stomach, causing thickening and rigidity of the gastric wall, called linitis plastica, and malignant cells often have a signet ring appearance [70].

In addition to the rare but highly penetrant genes described above, there is growing evidence that more common, but less penetrant, genes may account for a significant proportion of hereditary breast cancer. Both candidate gene and genome-wide searches have been used to identify low-penetrance polymorphisms that alone or in combination are associated with breast cancer. The identification and location of these breast cancer genes will ultimately permit further investigation of the precise role they play in cancer progression and will allow us to determine the percentage of total breast cancer caused by the inheritance of mutant genes. This, in turn, will ultimately enrich our understanding of all breast cancer, sporadic as well as hereditary, and will improve the identification of high-risk individuals.

With the growing awareness of the familial nature of breast cancer, increasing numbers of family members of women diagnosed with breast cancer are seeking information and advice about the disease, their potential risk, and available risk-reducing options. Women who seek counseling are often highly motivated by a personal experience with cancer in their family and by concern for the risks faced by themselves and their close relatives. As physicians become more aware of the importance of family history in determining a woman’s risk for breast cancer, they are increasingly referring their patients for cancer risk counseling. Even those individuals who are not candidates for genetic testing will benefit from having a realistic estimate of their cancer risk. In addition to providing risk information and risk counseling to the individual concerned about her risk for cancer, the process often has wide-reaching implications for the family and may ultimately extend to include additional family members.

Historically, the medical genetic counseling team has consisted of a medical geneticist, a genetic counselor, and, to a lesser extent, the referring primary care physician. As the field of genetic counseling has expanded to include adult diseases such as cancer, other disciplines, including oncology, gynecology, molecular genetics, social work, and psychology, have joined the team in order to provide the multidisciplinary approach needed.

There is also a growing interest in genetics on the part of nurses, many of whom are beginning to seek specialized training in the field. Genetic counselors and nurses trained in genetics are now increasingly delivering medical and genetic risk information about familial forms of cancer and counseling individuals and families about disease risk and management. Originally, cancer risk counseling programs were mainly situated in cancer centers and academic institutions, but these services are expanding to community hospitals, worksites, and health centers where they are often one component of a more broad-based health promotion program.

The genetic counseling process begins with the collection of several components of information. The first step in evaluating a woman’s risk for breast cancer is to evaluate her worries, questions, concerns, beliefs, and reasons for seeking counseling to guarantee that personal needs and priorities will be met in the counseling process. It is important at this early stage of counseling to establish a mutual trust and to negotiate a mutually agreeable agenda between the counselor and the individual seeking counseling. The counselor attempts to assess whether the individual’s expectations of cancer risk counseling are realistic. An exploration of the patient’s current knowledge of genetics, beliefs about the causes of cancer, and experiences with cancer can help to guide and personalize the session and ensure the clinician tailors their information for the patient. Throughout the course of the counseling process, the potential for psychological impact should be assessed and addressed. This includes evaluating for depression or anxiety, patient coping mechanisms and resilience, and available support systems (see Table 9.2). If necessary, referrals to mental health-care professionals should be provided [63].

An expanded family pedigree that includes first-, second-, and third-degree relatives (parents, siblings, children, half-siblings, aunts, uncles, grandparents, cousins, etc.) using standard human pedigree nomenclature [74] begins the process of estimating cancer hereditary risks. Both maternal and paternal history should be evaluated for types of cancer, bilaterality, pathology, ages at diagnosis and/or death, and history of risk-reducing steps, such as chemoprevention or surgeries [75]. Ancestry/ethnicity and consanguinity information are also important when calculating likelihood of a genetic risk, because specific mutations (i.e., founder mutations) occur with increased frequency in certain populations.

It is important to include all relatives, both affected and unaffected, in the family history in order to judge the degree of penetrance of the disease. In the case of hereditary breast cancer, it is also important to document cases of ovarian and other cancers in the family. Limitations to family history, such as small family size, unknown history and adoption, early deaths precluding the possibility of developing adult-onset diseases, prophylactic surgeries which remove an organ from subsequent risk of cancer, or few family members of the gender most affected by the cancer syndrome risks, e.g., few women in a family at risk for hereditary breast ovarian cancer (HBOC) syndrome, can challenge the clinician’s ability to estimate hereditary risk [76]. Reported family histories may be inaccurate, and confirming documentation, such as pathology reports, should be obtained when possible [77, 78].

Family history data is then graphically represented on a pedigree, which follows standard nomenclature to illustrate family relationships and disease information in graphical format (Fig. 9.6). The hallmarks of features of a family history which suggest a hereditary pattern include multiple cancers in close relatives, multiple cancers in a single individual, multiple cancers across generations, early age of onset of cancer, bilateral cancer in paired organs (e.g., breast), the presence of precursor lesions known to be associated with the cancer phenotype, and ancestry [72] (see Table 9.3).

The patient’s personal medical history should also be ascertained at this time, including prior medical conditions, cancer diagnoses, and treatments. Additional information about carcinogen exposure, reproductive history, hormone use, lifestyle factors, and previous breast biopsy history will influence estimates of cancer risk. A record of past cancer screening practices establishes a history of health promotion behavior and will help guide the counselor in making reasonable and appropriate health recommendations. Physical findings associated with a hereditary breast cancer syndrome can also be evaluated during the risk assessment session [75]. In the absence of a clinician qualified to evaluate physical features, appropriate referrals to specialists should be made, e.g., dermatologic assessment of features of Cowden syndrome [61]. Beyond the data obtained during the creation of the family tree, this process allows the clinician to assess the client’s emotional state, become aware of family dynamics and level of support, and set the tone for the session [79]. This part of the session can also provide information about a patient’s perception of risk, which may be influenced by cultural and ethnic identity, family interaction, personal experience with the condition, and spirituality [79].

The objective of risk communication is to provide patients with accurate information to help them understand and interpret their risk in order to make informed decisions about genetic testing and/or medical management [63]. Risk communication is particularly challenging in cancer genetic counseling due to the sheer number of different risks being shared with the patient (see Table 9.4).

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