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11 Cancer Worry: The Pedigree as a Psychosocial Tool
MODELS FOR PREDICTING THE RISK OF DEVELOPING CANCER OR THE PROBABILITY
such as mammography reliably identify cancer in relatives? A person who is undergoing cancer risk assessment needs to be able to tell his or her family story (Schneider,
2002). Taking time to listen to worries about developing cancer can help the clinician
understand the patient’s concerns about the effectiveness of cancer screening and
The clinician can also be alerted to signiﬁcant correlations between the patient’s
feelings and actions and his or her family history. For example, the patient may
seek aggressive prevention strategies such as prophylactic mastectomy or colectomy
because a parent or sibling did not survive their cancer. The patient may be more
anxious about participating in cancer screening as he or she approaches the age at
which a relative developed cancer, or even become more complacent about cancer
screening because he or she has passed the age at which the relative developed
cancer and thus has “escaped” the disease. A woman may fear becoming pregnant
because a relative was diagnosed with cancer in her pregnancy. If multiple relatives
have developed cancer, the patient may feel that cancer is the norm rather than the
exception (Patenaude, 2005).
Almost everyone who has a relative with cancer worries that the cancer in that
person may be inherited, placing them at risk for cancer as well. Overestimation of
cancer risk is common in both people who have a hereditary risk and those for whom
there is little evidence that there is high risk for cancer (Patenaude, 2005). A pedigree
can be used as a tool to educate the patient about cancer risks, as well as relieve
anxieties about risk for cancer in the absence of signiﬁcant family history factors.
5.12 MODELS FOR PREDICTING THE RISK OF DEVELOPING
CANCER OR THE PROBABILITY OF TESTING MUTATION-POSITIVE
FOR AN INHERITED CANCER SYNDROME
The development of models that factor family history into the likelihood of developing
cancer or the likelihood of having a positive test for a cancer genetic syndrome are
becoming readily available (NCI, 2009). Most of the models factor in the age at cancer
diagnosis of the consultand and in closely related relatives. The models predicting
breast cancer risk or the likelihood of having a BRCA1 or BRCA2 mutation are
more advanced as compared to other cancer syndromes. Each model has it ﬂaws, but
certainly they each can be useful in a clinical setting (Barcenas et al., 2006; Jacobi
et al., 2008; Kang et al., 2006). The Claus model is useful for predicting breast cancer
risk for women with one or two ﬁrst- or second-degree relatives with breast cancer
(Claus et al., 1994). This model considers the current age of the woman and the ages
at which her ﬁrst- and second-degree relatives developed cancer. It does not consider
ovarian cancer, male breast cancer, or bilateral breast cancer. Figure 5.1 illustrates
how signiﬁcantly a younger age at breast cancer diagnosis positively inﬂuences a
ﬁrst- or second-degree relative’s likelihood of developing breast cancer (with the risks
being higher for breast cancer diagnosed before menopause). The Gail model has been
used primarily for postmenopausal women who have a limited family history of breast
cancer. This model does not factor in the age that the relatives developed breast cancer,
Figure 5.1 The empirical risk to develop breast cancer based on the age of onset of breast cancer in a mother and a maternal aunt. Note that if the
consultand’s mother and aunt develop breast cancer between the ages of 70 and 79 years, the consultand’s lifetime risk to develop breast cancer is
similar to the background risk to develop cancer by age 80. Risk ﬁgures derived from Claus et al. (1994).
only the number of ﬁrst-degree relatives with breast cancer. Other personal factors
such as the age of the women, age at ﬁrst live birth, ethnicity, and breast biopsies
are also factored into the model. This model can underestimate hereditary risk. The
Myriad-Frank model is derived from the family history information regarding the age
and types of cancer in the consultand and his or her ﬁrst- and second-degree relatives
listed on requisition forms from persons undergoing the commercial test for BRCA1
and BRCA2 through Myriad Genetics Laboratory (www.myriadtests.com), and they
have developed a similar model in relation to persons undergoing genetic testing for
The National Cancer Institute website (at http://riskfactor.cancer.gov/cancer
risk prediction) is a comprehensive resource with links to summaries of many of the
cancer risk assessment models and related bibliographies. Another essential resource
is the BayesMendel Lab (2009) (http://astor.som.jhmi.edu/BayesMendel/index.html),
which includes references on cancer susceptibility and links to models for predicting who may carry a cancer susceptibility gene (all open source software). Models
such as these are likely to play a growing role in determining which persons are
the best candidates for genetic testing and for whom increased cancer surveillance
is indicated based on family history alone when the available genetic tests do not
identify all of the possible mutations. Although the models’ predicting the likelihood
of identifying a cancer susceptibility mutation or for predicting the risk for cancer
can be useful in aggregate, the models give widely varying predictions (Jacobi et al.,
2008). Therefore, an understanding of the assumptions used in creating each model
and the appropriate clinical application is essential.
The instruments of molecular genetics, in concert with a precise genetic family
history, provide clinicians with powerful investigative tools to identify individuals
with an increased risk to develop various cancers. Corroborating verbal history of
cancer with medical records is key so that accurate cancer risk assessment and a plan
for genetic testing and cancer screening and prevention can be implemented. Verbal
recall of cancer diagnoses is less likely to be accurate on distant relatives and for
female cancers and rare cancers.
For most men and women with a personal or family history of cancer, counseling about cancer screening and prevention will rely on a through assessment of the
family history rather than a genetic test result. With the ever-expanding palette of
commercially available tests that predict cancer susceptibility, medical professionals must be prepared to offer accurate counseling about the meaning of a positive,
negative, or ambiguous test result. Testing, if performed, must be interpreted in the
context of the family history. It is irresponsible to order a cancer genetic test without
taking a medical family history. Such testing, done poorly, can cause more harm
than beneﬁt. Test results have profound reverberations for an individual’s psychological and physical health, insurability, and family and social functioning (Greely,
1997; McKinnon et al., 1997; Patenaude, 2005; Schneider, 2002; Trepanier, 2004).
USING A PEDIGREE TO RECOGNIZE INDIVIDUALS WITH AN INCREASED SUSCEPTIBILITY
Cautions Dr. Kenneth Ofﬁt (1998), former chair of the American Society of Clinical
Oncology’s Subcommittee on Genetic Testing for Cancer Susceptibility, “A genetic
test of outstanding scientiﬁc interest is of little clinical value if the clinician is unable
to interpret it, the patient afraid or unsure how to act on it, and the national health-care
system unable to provide it without penalty or discrimination.”
A dramatic example of the power of pedigree analysis is shown in Figure 5.1. A
healthy 29-year-old woman is concerned about her risk of developing breast cancer
given a history of breast cancer in her mother and maternal aunt, with no other
family history of breast or other cancers. The occurrence of postmenopausal breast
cancer in her aunt and mother does not signiﬁcantly change her risk to develop breast
cancer from that of other women her age. In contrast, the consultand’s lifetime risk
to develop breast cancer (based on empirical risk ﬁgures from the Claus model)
approaches that of an autosomal dominant syndrome if her mother and aunt have
breast cancer diagnosed in their 30s (Claus et al., 1994). For many individuals with
fears about a family history of cancer, careful pedigree analysis can reassure them that
their lifetime risk to develop cancer is not signiﬁcantly different from other people
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