J Pediatr Adolesc Gynecol (2010) 23:253e258

Tips for Clinicians

Hereditary Breast and Ovarian Cancer Syndrome and Issuesin Pediatric and Adolescent Practice

Jonathan D. Herman, MD1,2, and Heather Appelbaum, MD1,2

1Obstetrics & Gynecology and Women’s Health, Albert Einstein College of Medicine of Yeshiva University; 2Department of Obstetrics and

Gynecology, Long Island Jewish Medical Center, Department of Obstetrics and Gynecology, Long Island Jewish Medical Center/Alexandraand Steven Cohen Children’s Medical Center of New York, New Hyde Park, New York, USA

Key Words. Hereditary breast and ovarian cancersyndrome (HBOC)dBRCAdBRCA1dBRCA2dPediatricsdAdolescentsdGenetic counselingdBreastcancer screeningdOvarian cancer

Concerns for Pediatric and Adolescent Patients

Hereditary breast and ovarian cancer syndrome(HBOC) is responsible for most hereditary breastand ovarian cancers. As an inheritable genetic disor-der, parental carrier status unequivocally impacts thepediatric and adolescent patient population. Childrenwhose parents are genetic carriers of mutations ineither of the tumor suppressor genes, BRCA1 orBRCA2, which are responsible for the majority ofHBOC, invariably have concerns regarding their par-ents’ health. Children at risk for HBOC may be addi-tionally concerned about the future of their ownbreasts and ovaries with respect to cancer risks,screening and surveillance, risk reducing prophylacticoptions, and future fertility. Misconceptions, fears,and lack of accurate information may contribute toa distorted body image, cause inappropriate anxiety,and have a negative psychological impact in the pedi-atric patient. Parents with known carrier status oftenexpress concerns for the future well-being of theirchildren. Pediatric practitioners must be able to ad-dress these concerns and make appropriate recom-mendations for genetic testing for the pediatric andadolescent patient population. Practitioners will bemore capable of addressing these concerns if theyare able to accurately identify families at risk forHBOC, determine appropriate timing of testing for

Address correspondence to: Jonathan D. Herman, MD, 2500 Mar-cus Ave, New Hyde Park, NY 11042; E-mail: jdherman@gmail.

com

� 2010 North American Society for Pediatric and Adolescent GynecologyPublished by Elsevier Inc.

young adults at risk for HBOC, and understand theethical, psychological, and clinical implications oftesting for HBOC.

What Is HBOC?

Women with HBOC represent a small but significantproportion of all women with breast and ovarian cancer.One in eight (12%) of U.S. women 90 years of age oryounger will develop breast cancer and one in 70(1.4%) will develop ovarian cancer. The AmericanCancer Society estimates for 2009, approximately192,370 women and 2000 men will have breast cancerand approximately 21,550 women will have ovariancancer in the United States. Family history and ageare the two greatest risk factors for both breast cancerand ovarian cancer. With current treatment options, ap-proximately 80% of women survive breast cancer whilenearly 75% will succumb to ovarian cancer.1

Although continually overestimated by the generalpopulation, only 5e10% of breast cancers and approx-imately 10% of ovarian cancers are hereditary.2e4 In1994 and 1995, two of the most important genesresponsible for HBOC were sequenced and designatedBRCA1 and BRCA2. BRCA1 and BRCA2 function asDNA repair genes. Deleterious mutations in eitherBRCA1 or BRCA2 are responsible for and can be uti-lized to identify most cases of HBOC. Estimates iden-tify BRCA1 and BRCA2 mutations as responsible forabout 80e85% of hereditary breast and ovarian can-cers.5,6 Other identified genes include PTEN associatedwith Cowen Syndrome, p53 associated with Li-Fraumeni Syndrome, and STK11 associated withPeutz-Jeghers Syndrome.7

When a BRCA1 mutation is present, the reportedrisk of developing breast cancer by the age of 70 is ashigh as 87%. For a BRCA2 mutation, the risk of breastcancer is as high as 56%.8e11 Furthermore, the

1083-3188/$36.00doi:10.1016/j.jpag.2010.02.004

Table 1. Risk Factors for Hereditary Breast and Ovarian Cancer

Syndrome

Risk Factors for HBOC

� Breast cancer under age 50� Ovarian cancer at any age� Ashkenazi Jewish Ethnicity� Bilateral breast cancer� A second primary breast cancer� Male breast cancer� A family member who is BRCA positive

254 Herman and Appelbaum: Hereditary Breast and Ovarian Cancer Syndrome

recurrence risk for the BRCA positive patient alreadydiagnosed with breast cancer may be as high as 50%,compared to 10% for the BRCA negative breast cancerpatient.12 The ovarian cancer risk is 40% or more forBRCA1 and 22% for BRCA29,11(See Fig. 1).

Early onset breast cancer is noted in many familieswith HBOC. The diagnosis of breast cancer in theBRCA positive patient may begin as early as age 25.This is much younger than for those diagnosed withnonhereditary breast cancer. The age distribution ofovarian cancer parallels the nonhereditary ovarian riskbeginning at the end of the fourth decade of life.

Who Is At Risk for HBOC?

BRCA testing is not utilized for general populationscreening. Hereditary screening is indicated in familiesthat have a strong history of breast and/or ovarian can-cer. An attempt should always be made to test affectedfamily members. However, the affected members maynot be readily available for testing. Careful assessmentof personal and family history should guide cliniciansto appropriate patient selection and timing of testing.Families with a history of premenopausal breast cancer,male breast cancer diagnosed at any age, or ovariancancer diagnosed at any age should be offered testing.HBOC is 12.5 times more common in the AshkenaziJewish population. Ashkenazi Jewish descent is consid-ered a significant risk factor for BRCA (See Table 1).

The American Society of Clinical Oncology (AS-CO) recommends that genetic testing be offered whenan individual has a personal or family history sugges-tive of a genetic cancer susceptibility and that testingshould be performed only when results may influencepatient management or management of family mem-bers at risk for hereditary cancer.13. The American Col-lege of Obstetricians and Gynecologists (ACOG)Committee Opinion on breast and ovarian cancerscreening recommends offering BRCA mutation test-ing to families in which two or more members havehad breast or ovarian cancer or in which a BRCA muta-tion has been found.14 Published guidelines are alsoavailable from the American Medical Association,15

Fig. 1. BRCA mutations increase breast and ovarian cancerrisk.

the American Society of Breast Surgeons,16 the Amer-ican Society of Clinical Oncology,15 the National Com-prehensive Cancer Network,17 the Oncology NurseSociety, the Society of Gynecologic Oncologists,18

the Society of Surgical Oncology,19 the AmericanCollege of Obstetrics and Gynecology,16 and the U.S.Preventive Services Task Force.20

BRCA testing provides the practitioners with anopportunity to better manage their patients and familymembers by assigning an accurate statistical riskmodel. These results will help the patient makeinformed risk management decisions by understandingtheir individual breast and ovarian cancer risk. Testingwill impact each family member, but the results allowfor individualized medical and psychological manage-ment. As part of the pretest counseling, the patient mustbe educated with adequate and accurate informationbecause testing raises important medical, psychologi-cal, ethical, and social issues not only for the patientsthemselves but also for their family members. ASCOissued a basic guide to molecular susceptibility test-ing.15 ASCO suggests that issues discussed duringcounseling include, but are not limited to:

1. Clarification of the patient’s increased risk status;2. Explanation of how genetics affects cancer

susceptibility;3. Potential benefits, risks, alternatives, and limita-

tions of testing;4. Possible outcomes of testing (e.g., positive, neg-

ative, or uncertain test results);5. Limited data regarding efficacy of methods for

early detection and prevention;6. Possible psychological and social impact of

testing;7. Alternatives to molecular susceptibility testing;8. Counseling regarding therapeutic options; in-

cluding discussions which address the limitationsof these options.

Psychosocial Impact of BRCA Testing

Parents often discuss their own test results and treat-ment plans with their children. Additionally, childrenobserve their parents’ physical and psychological

255Herman and Appelbaum: Hereditary Breast and Ovarian Cancer Syndrome

reaction to the diagnosis and treatment. It will be advan-tageous for the pediatric healthcare providers to be-come familiar with the medical aspects of HBOC andrelated pediatric psychosocial issues.

While most patients do not exhibit long-termpsychological effects, counseling by a knowledgeablehealthcare professional has been shown to decreaseanxiety in the at risk patient.21 In contrast, others sug-gest that BRCA testing may cause the patient additionalanxiety and/or depression.26 Lerman et al reported thatfamily members may benefit from education and coun-seling but should be monitored for potential adverse ef-fects.22,23 Symptoms of anxiety and depression maymanifest prior to the counseling period, during counsel-ing, and after results have returned. Counseling prior totesting and the availability of counselors in an ongoingmanner has been shown to be of significant benefit.14

Future investigations will be necessary to assess theaffect of counseling on children and adolescent familymembers.

At the 2009 Annual Meeting of the American Societyof Clinical Oncology, Bradbury et al presented a studyfrom the Fox Chase Cancer Center addressing BRCApositive patients parental perceptions on the impact oftheir own BRCA status as it relates to their children.Bradbury et al found that most parents share their BRCAresults with their children. Overall, the majority of par-ents reported that their children handled the informationwell, although negative reactions were more frequentamong certain subgroups including younger childrenand those of parents with a mutation or a variant of un-certain significance.25 Most parents do not perceive theirchildren to have adverse reactions to this information.The study was limited by the size of the population stud-ied. Larger studies are needed to address the accuracy ofparental reporting with respect to childhood responses tofamily related BRCA carrier status.

Tercyak et al reported that children growing up in he-reditary breast cancer families might experience dimin-ished psychological well-being.26,27 In addition tocoping with cancer-affected parent or close relatives,these children may focus on their own health risks.While knowledge of a parent’s BRCA1/2 negative sta-tus may allay a child’s concerns about cancer, otherscould experience distress due to positive test results.Children with more psychological distress symptomsdid experience more frequent thoughts of becomingsick and had greater cancer worries. Learning of a par-ent’s positive test result could exacerbate these tenden-cies and precipitate adolescent inquiries as to their owngenetic status.

Further studies are needed to define the short andlong term effects of BRCA testing for different agegroups. These studies must involve both parents andchildren in order to further clarify the possible psycho-social responses upon learning of hereditary risk during

childhood. Intervention strategies by healthcare profes-sionals in the pediatric population should be evaluated.

Medical Options for Patients with HBOC

Surveillance, chemoprevention, and risk reducing sur-gery are offered to patients who test positive forBRCA.24 Breast surveillance includes monthly breastself-examinations, clinical breast exams biennially, an-nual mammography and breast MRI beginning at age25e30. Although this does not decrease the risk of de-veloping breast cancer, increased surveillance potenti-ates early detection and thus implicates decreasedmorbidity and mortality. Risk reducing measures in-clude chemoprevention with selective estrogen recep-tor modulators or risk reducing bilateral mastectomywith or without breast reconstruction.

Ovarian cancer surveillance is controversial and itsvalue has been questioned. Serial CA-125 analysis cou-pled with transvaginal ultrasound plus color Dopplerstudies have been suggested, but the clinical utilityremains poor.28e31 Risk reducing bilateral salpingo-oophorectomy (BSO) after 35 years of age and aftercompletion of childbearing has been shown to decreasethe risk of ovarian cancer, fallopian tube cancer, andbreast cancer. There is no benefit of prophylacticBSO prior to age 35 because hereditary ovarian canceris extremely rare prior to age 35. A prophylactic BSO, ifperformed prior to menopause, reduces the risk ofbreast cancer by approximately half and ovarian cancerby greater than 90%.32

The use of oral contraceptive pills (OCP) in patientswith HBOC or a family history of HBOC has not beendirectly addressed, although several studies have exam-ined the risk of breast cancer and/or ovarian cancer withrespect to usage of oral contraception. Narod et al re-ported that the use of OCPs for six years or more re-duces the risk of ovarian cancer by as much as 60%.Other authors have not been able to reproduce these re-sults.33 While risk reduction for ovarian cancer in re-sponse to oral contraceptive usage has not beenclearly demonstrated, certainly usage of OCPs is notcorrelated with an increased risk of ovarian cancer.Although many patients believe oral contraceptive us-age can adversely affect one’s risk of breast cancer,there are no well designed studies that support an in-crease in breast cancer. In fact, the National Institutefor Child Health and Human Development Women’sContraceptive and Reproductive Experiences Study ex-amined the risk of breast cancer in over 4,500 womenwho used OCPs and found no significant increased riskof breast cancer.34 Narod reported that there is a slightrisk increased risk of breast cancer for BRCA1 muta-tion carriers who used OCPs while BRCA2 carriersshow no increase.35

Table 2. Recommendations for BRCA testing By Age

Recommendations for BRCA testing

AGE Is BRCA testing indicated? Does Positive BRCA status changetreatment recommendations?

Is there psychological benefit to testing

!18 years no no maybe18-25 years maybe no yesO25 years maybe yes yes

256 Herman and Appelbaum: Hereditary Breast and Ovarian Cancer Syndrome

Recommendations for the Pediatric and Adoles-cent Patient

Pediatric practitioners can anticipate parental and indi-vidual requests for testing of their patients. Consider-ation of cancer risk in addition to the medical andpsychological benefit of testing for BRCA mutationsis essential in order to determine if testing is warranted.Currently, there are no guidelines which dictate appro-priate timing for the counseling and testing of the at riskpediatric patient. Testing raises important medical, eth-ical, psychological, and social issues for the pediatricand adolescent patient that differ from those of theadult. In effort to address potential age-related contex-tual differences, patients may be stratified based on age.

For patients up to 18 years of age, there are no rec-ommendations for alteration in medical management,because the risk of breast and ovarian cancer remainsextremely low to negligible. Some would suggest thatit is unethical to test patients in this group because thepatients cannot receive proper counseling and informedconsent and medical management will not be affectedby test results. The concept of ‘‘earliest onset of diseaseor illness’’ is applied.36 One should begin to test only atthe age when disease or illness begins. Arguably, par-ents are the guardians of their children and thereforecould make custodial medical decisions as their child’ssurrogate. In the hope of a negative result, parents mayrequest testing on behalf of their children in order tohave the information for future treatment planningand to decrease their own anxiety of passing a mutatedgene to their children. Nevertheless, no medical societyor association supports testing for HBOC in this agegroup (see Table 2.)

For patients 18e25 years of age, there are no recom-mendations for alteration in medical management withrespect to surveillance, prophylactic interventions, orusage of OCPs and the risk of breast and ovarian cancerremains extremely low to negligible. Testing providesinformation that may increase or decrease a patient’spsychological burden. Nevertheless, the patient, nowin majority, may be properly counseled and consented.Obtaining a result is informative and, whether positiveor negative, the information may allow the at-risk pa-tient to resolve an increase of anxiety due to the ‘‘fearof the unknown.’’ Testing for the BRCA mutations inthis age group may be acceptable (see Table 2.)

For patients age 25 and older, surveillance should beincreased, prophylactic measures will be considered,and fertility plans may be affected. Medical manage-ment decisions would now be altered based on BRCAresults. Testing provides information that may increaseor decrease a patient’s psychological burden and thepatient, now in majority, may be properly counseledand consented. Counseling for patients at risk forHBOC in this age group should be mandatory and test-ing is acceptable and appropriate (see Table 2). Futurewell designed studies are necessary to elucidate the ef-fects of testing in the pediatric and adolescent popula-tion and define age specific parameters for testing.

Identification of At Risk Families

Pediatric, adolescent, and gynecologic professionalsare in a position to identify families that may benefitfrom HBOC screening. Just over 10% of women iden-tified as high risk for HBOC report having discussedgenetic testing with a health professional. Fewer than5% were advised by a health professional to be testedand fewer than 2% actually underwent testing .37 TheAmerican College of Obstetrics and Gynecology rec-ommends that screening for HBOC should be a routinepart of every gynecologic practice. Every patientshould be screened through the use of a personal andfamily history.16 The American Academy of FamilyPhysicians recommends that women whose family his-tory is associated with an increased risk for deleteriousmutations in BRCA1 or BRCA2 genes be referred forcounseling and evaluation for BRCA testing.38

Although the American Academy of Pediatrics hasnot commented on HBOC and BRCA testing, the pedi-atrician interacts with both patient and family memberand is well positioned to identify families that may haveHBOC. When those families are identified, they shouldbe referred for formal counseling. In this respect, pedi-atricians can act as a gateway for referral of entire fam-ily for appropriate risk evaluation.

Key Points

� Pediatric and adolescents providers should beaware of family cancer syndromes including he-reditary breast and ovarian cancer syndrome.

257Herman and Appelbaum: Hereditary Breast and Ovarian Cancer Syndrome

� Pediatric and adolescent providers should be alertto the pediatric patient’s psychological responsetowards a parent with a positive carrier status.� Pediatric and adolescent providers should recog-

nize that family history of HBOC may impactbody image, cause anxiety, and contribute to psy-chological distress in children and adolescents.� Pediatric and adolescent providers should be ad-

vised that testing for the pediatric patient shouldbe discouraged before the age of 18 because theresults will not affect medical management or pre-ventive health care strategies for this age group.� The pediatric and adolescent provider are well

positioned to identify families that are at riskfor hereditary breast and ovarian cancer and referthem for proper evaluation.� Further research will define appropriate parame-

ters and interventions that healthcare profes-sionals may employ to help guide their pediatricand adolescent patients.

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