LOCAL-REGIONAL EVALUATION AND THERAPY (KK HUNT, SECTION EDITOR)

Genetic Counseling and Genetic Testing in the PreoperativeEvaluation of Breast Cancer Patients

David Euhus & Linda Robinson

Published online: 11 February 2012# Springer Science+Business Media, LLC 2012

Abstract Breast cancers arising in the context of germlineBRCA gene mutation have unique biological features that mustbe considered during treatment planning. Breast conservingsurgery is an acceptable option in highly motivated womenwho are fully informed about the risks of ipsilateral breast tumorrecurrence and contralateral breast cancer. Partial breast irradia-tion is not recommended for these women. Concurrent bilateralsalpingo-oophorectomy should be considered. BRCA1-associated breast cancer may be resistant to taxanes, but appearshighly sensitive to platinum agents and to PARP inhibitors.Preoperative genetic testing can be accomplished with shortturn around times and does not increase patient anxiety. Inclu-sion of a professional genetic counselor in the managementteam is essential. BRCA gene mutation status is emerging asan important prognostic and predictive factor for breast cancerpatients. Preoperative genetic counseling and testing is recom-mended for women likely to carry a BRCA gene mutation.

Keywords BRCA1 . BRCA2 . Breast cancer . Genetictesting . Genetic counseling . Breast conserving surgery .

Mastectomy . Bilateral salpingo-oophorectomy .

Hysterectomy . Preoperative . Chemotherapy . Radiation .

PARP inhibition . Cisplatin . Anxiety . Ipsilateral breast tumorrecurrence . Contralateral breast cancer . Survival .

Recurrence . Tamoxifen

Introduction

Germline mutations in BRCA1 or BRCA2 account for 5%to 7% of breast cancers in the United States. Individualswho carry a deleterious mutation in BRCA1 or BRCA2have unique cancer risk profiles that distinguish them fromthe general population both in terms of timing and types ofcancer events. In addition, breast cancers that arise in thecontext of a deleterious BRCA1 or BRCA2 gene mutationhave unique biological features that can influence treatmentdecisions. From a personalized cancer medicine perspective,genetic testing can provide one of the most treatment-relevant classifier strategies available. Nevertheless, mostpatients and many clinicians still ask, “What is the senseof testing? What can be done with a positive result?”Additional concerns about preoperative genetic testingcenter on information overload at the time of initialdiagnosis, treatment delays while waiting for a geneticcounseling appointment and then while waiting for agenetic test result, and fears of genetic discrimination.This review examines the issues surrounding preoperativegenetic counseling and testing in newly diagnosed breastcancer patients.

BRCA Gene Mutation and Breast Cancer Prognosis

Existing literature comparing distant disease-free and over-all survival between BRCA-mutated and sporadic breastcancer patients is quite heterogeneous and no consistenttrends are observed [1, 2•]. However, a recent meta-analysis does suggest that 5-year progression-free (ipsi-lateral breast and distant sites) and overall survival aresignificantly reduced in BRCA1 mutation carriers but notBRCA2 carriers [3]. This would be expected as nearly80% of BRCA1 mutation-associated breast cancers are triple-negative, basal-type breast cancers, whereas approximately

D. Euhus (*)Department of Surgery and Simmons Comprehensive Cancer Center,University of Texas Southwestern Medical Cancer,5323 Harry Hines Blvd.,Dallas, TX 75390-9155, USAe-mail: David.euhus@utsouthwestern.edu

L. RobinsonSimmons Comprehensive Cancer Center, Cancer Genetics,University of Texas Southwestern Medical Center,5323 Harry Hines Blvd,Dallas, TX 75390-9161, USAe-mail: Linda.robinson@utsouthwestern.edu

Curr Breast Cancer Rep (2012) 4:102–109DOI 10.1007/s12609-012-0071-y

75% of BRCA2 mutation-associated breast cancers arehormone sensitive.

Likewise, the risk of ipsilateral breast tumor recurrence(IBTR) among BRCA mutation carriers undergoing breastconserving surgery is inconsistent in the literature, withmany studies suggesting that there is no increased risk [1].However, a retrospective study limited to women 42 yearsof age or younger reported IBTR rates approaching 4% peryear [4], and this is the rate we use when counseling veryyoung women. Other studies have reported local recurrencerates ranging from 1.7% to 2.7% per year [2•, 5], valueswhich are greater than the 1% per year rate traditionallyquoted for sporadic breast cancer patients.

One point on which the literature is quite consistent isthat BRCA gene mutation carriers are at significantly in-creased risk for contralateral breast cancers [1]. This riskranges from 2.0% to 6.2% per year, which is considerablyhigher than the 0.8% per year rate typically quoted forsporadic breast cancer patients and the 0.3% per year ratefor hormone receptor-positive breast cancer patients treatedwith adjuvant hormonal therapies [6, 7]. There is someevidence that BRCA1 mutation carriers face higher contra-lateral breast cancer risk than BRCA2 carriers [8].

In addition, BRCA gene mutation carriers face a 15% to60% lifetime risk for ovarian cancer, a cancer that is muchmore difficult to diagnose at an early, curable stage thanbreast cancer. Knowing that a patient carries a deleteriousBRCA gene mutation early in the course of primary breastcancer treatment permits a more informed discussion oftreatment options and provides an opportunity to proactivelyassess and manage associated risks.

Primary Surgery Decisions

Breast Conservation Versus Mastectomy

Partial mastectomy followed by adjuvant whole breast radi-ation therapy in BRCA gene mutation carriers is associatedwith the same regional and distant recurrence rates and thesame breast cancer-specific and overall survival as mastec-tomy [1, 2•]. For this reason alone, breast conservationremains a reasonable option for the well-informed, highlymotivated BRCA gene mutation carrier. Discussion of IBTRrisk should consider the patient’s age (younger patients havehigher rates [4]), the mutated gene (BRCA2 patients mayhave higher IBTR rates than BRCA1 patients [2•]), andplans for systemic adjuvant chemotherapy which has beenshown to reduce IBTR [2•]. The patient also needs tounderstand that she is at high risk for contralateral breastcancer events, but if her tumor is estrogen receptor positive,adjuvant hormonal therapy is likely to reduce this risk by50% [9–11].

There are no prospective studies showing improved sur-vival for BRCA gene mutation carriers who opt for bilateralmastectomy at the time of primary breast cancer diagnosis.This option will, however, significantly reduce the risk ofIBTR and contralateral breast cancer. There is a notabletrend for increased rates of bilateral mastectomy evenamong sporadic breast cancer patients. This is largely apatient-driven phenomenon and may be accelerated by re-cent advances in mastectomy and reconstruction techniques.Retrospective data have suggested that bilateral mastectomyis associated with improved breast cancer-specific survivalfor younger women (< 50 years of age) with hormonereceptor-negative breast cancer [12] and for women withfamily histories of breast cancer [13].

Bilateral Salpingo-Oophorectomy

Bilateral salpingo-oophorectomy (BSO) has been recog-nized as an effective adjuvant therapy for some premeno-pausal breast cancer patients for more than a century [14].For BRCA gene mutation carriers, BSO reduces the inci-dence of primary breast cancer by about 50% and the risk ofovarian cancer by 80% to 96% [15–18•]. Although BSOmay provide some therapeutic benefits to some patients withBRCA gene mutation-associated breast cancer, availabledata are quite limited and not consistently positive. Forexample, a recent study that included 302 breast cancercases from 9 centers reported that BSO did not significantlyreduce the rates of IBTR, contralateral breast cancer, ordistant recurrence [2•]. Conversely, a Prevention and Obser-vation of Surgical Endpoints (PROSE) study that included1060 breast cancer patients reported that although BSO didnot reduce the risk of second primary breast cancers, it wasassociated with a reduction in breast cancer-specific and all-cause mortality [19•]. Neither of these studies specificallyassessed the impact of premenopausal BSO. BSO cannotcurrently be considered standard of care for BRCA genemutation carriers recently diagnosed with breast cancer, butthe all-cause mortality signal from the PROSE study, whichwas strongest for BRCA1 mutation carriers, suggests that itshould be considered in initial treatment planning.

Whether the uterus should be removed or not at the timeof BSO is still controversial. Laparoscopic BSO is a mini-mally invasive procedure from which patients recover rap-idly. Adding a hysterectomy increases the operative timeand postoperative discomfort. However, we generally rec-ommend hysterectomy at the time of BSO because, forpatients with hormone-sensitive breast cancer, it permitsthe use of tamoxifen without the concerns of endometrialhyperplasia or endometrial cancer and also permits the useof estrogen replacement therapy without the addition of aprogestin. The former concern may be ameliorated by theavailability of aromatase inhibitors (AI). Even so, tamoxifen

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may provide a useful alternative for women experiencingsignificant bone loss or musculoskeletal symptoms on anAI. Although hormone replacement therapy (HRT) is gen-erally avoided in breast cancer patients, an early, abruptsurgical menopause can be associated with disabling qualityof life issues. Hormone replacement therapy may be re-quired in a small subset of patients and should not bewithheld. Concerns surrounding progestins in this settingare largely theoretical, as existing data on HRT after breastcancer are inconsistent [20] and there is evidence that pro-gestins do not diminish the primary prevention effects ofBSO in BRCA gene mutation carriers [21].

Combined Breast and Ovarian Surgery

Small case series suggest that bilateral mastectomy withor without immediate reconstruction can be combinedwith BSO with acceptable morbidity [22]. This requiresmulti-disciplinary coordination with breast surgery, plasticsurgery, and gynecology, which may cause some delaysin getting treatment started. This is our preferred ap-proach, however, and, in our experience most womenprefer a single anesthetic and hospitalization over astaged approach.

Radiation in BRCA Gene Mutation Carriers

BRCA1 and BRCA2 function in DNA double strand breakrepair. Radiation induces DNA double strand breaks that arenot efficiently repaired in cells from patients with BRCAgene mutations [23]. This might suggest that BRCA genemutation-associated breast cancers may be more sensitive totherapeutic doses of radiation. It might also suggest thatBRCA gene mutation carriers would be more susceptibleto the carcinogenic effects of sub-therapeutic doses of radi-ation. Side scatter to the contralateral breast may be oneconcern, but available data suggest that whole breast radia-tion delivered after partial mastectomy does not increase therisk of contralateral breast cancer in mutation carriers [2•, 4].Accelerated partial breast irradiation (APBI) delivers a ther-apeutic dose of radiation to the tumor bed with a fall-offgradient extending for several centimeters into the surround-ing tissue. This raises the concern that APBI may induce acarcinogenic zone in neighboring breast tissue. BRCA genemutation-associated breast cancer is currently classified as“Unsuitable for APBI outside of a clinical trial” [24]. Newimaging technologies, such as positron emission mammog-raphy and breast-specific gamma imaging, are gaining pop-ularity as alternatives to breast MRI for assessing extent ofdisease in newly diagnosed breast cancer patients. Theseimaging modalities expose patients to significantly higherradiation doses than diagnostic mammography [25]. Their

use in BRCA gene mutation carriers should be carefullyconsidered.

Systemic Treatment Decisions

Chemotherapy

Although surgery is the primary modality for achievinglocal and regional control, its ultimate impact on outcomeis modest for many tumors. Patients die of systemic disease,but modern hormonal therapies and chemotherapy signifi-cantly reduce recurrence and mortality in a subset ofpatients. Primary tumor features such as hormone receptorstatus or Her-2/neu amplification predict treatment responseand permit rational selection of patients for targeted thera-pies. BRCA gene mutation status is emerging as an addi-tional predictive marker. Neoadjuvant chemotherapy isgaining in popularity, even for operable breast cancer.Knowing a patient’s BRCA gene mutation status prior tothe start of chemotherapy can influence the selection ofagents and establish eligibility for clinical trials designedspecifically for mutation carriers.

Anthracyclines, taxanes, and cyclophosphamide are themost frequently used breast cancer chemotherapeutics and itis reasonable to ask whether the unique biological featuresof BRCA-mutated breast cancer, most notably defects inDNA double strand break repair, render them more or lesssusceptible to these agents. Anthracyclines are DNA inter-calating agents that interfere with the activity of topoisomer-ase and inhibit DNA synthesis. Retrospective data fromBRCA gene mutation carriers treated with anthracycline-based neoadjuvant chemotherapy consistently show thatthe pathologic complete response (pCR) rate amongBRCA1 carriers is similar to or greater than that observedamong sporadic cases, but responses in BRCA2 patients aremore variable [26–28]. Taxanes are microtubule stabilizersthat interfere with mitosis. One report suggested thatBRCA1-mutated triple-negative breast cancer is highly re-sistant to docetaxel in the metastatic setting [29], and anoth-er suggested low response rates for both estrogen receptor-positive and negative BRCA1 mutation-associated breastcancer in the neoadjuvant setting [30]. Cyclophosphamideis an alkylating agent that creates DNA damage throughcross-linking. BRCA mutated tumors with impaired DNArepair should be quite sensitive to DNA-damaging agents,but there are no studies specifically assessing the responseof these tumors to cyclophosphamide. Platinum agents arealkylating-like DNA damaging agents but are not common-ly used in breast cancer treatment. Studies in cell linessuggest that resistance to paclitaxel is directly correlatedwith sensitivity to cisplatin [31] and that loss of BRCA1 isassociated with cisplatin sensitivity [32]. Retrospective

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neoadjuvant data from 102 patients carrying Polish foundermutations in BRCA1 showed a 20% pathologic completeresponse (pCR) rate for anthracycline-based regimens ascompared to 83% to 90% for cisplatin [33•, 34].

Single strand DNA breaks are the most frequently occur-ring type of DNA damage. Single strand breaks are con-verted to double strand breaks when DNA is replicated.Because BRCA gene mutations are associated with im-paired DNA double strand break repair, agents that interferewith single strand break repair, such as inhibitors of poly(ADP-ribose) polymerase (PARP), are highly lethal toBRCA-associated breast cancers. An early phase 1 trial ofthe oral PARP inhibitor, olaparib, in patients with advancedtreatment-refractory cancers observed objective responses inBRCA mutation carriers only, including one durable com-plete clinical response in a breast cancer patient [35•]. Asecond phase 1 trial restricted to advanced or metastaticbreast cancer in BRCA gene mutation carriers recorded a50% objective response rate for BRCA1 carriers as com-pared to 22% for BRCA2 carriers at the 400 mg twice dailydose [36•]. Though PARP inhibitors are not currently ap-proved by the US Food and Drug Administration (FDA) forthe treatment of breast cancer, there are currently more thana dozen clinical trials open and accruing that target BRCAmutation carriers, many of which include PARP inhibition(http://www.ClinicalTrials.gov).

Hormonal Therapy

Adjuvant tamoxifen therapy has been shown to reduce therisk of contralateral breast cancer for both BRCA1 andBRCA2 gene mutation carriers [9–11]. There are some datato suggest that tamoxifen improves survival for BRCA1mutation carriers irrespective of hormone receptor status[37], an effect some have attributed to estrogen receptor-β[38], which is expressed in 44% of BRCA1-associatedtriple-negative breast cancers [39]. There are currently nodata concerning the effects of aromatase inhibitors on sec-ond primary breast cancers, distant recurrence, or survivalamong BRCA gene mutation carriers. Our current practiceis to restrict the use of hormonal therapies to hormonereceptor-positive breast cancers in BRCA mutation carriersand to treat them essentially the same as their sporadiccounterparts. This is an area clearly in need of additionalinvestigation.

Selecting Patients for Genetic Counseling and Testing

The foregoing makes the argument that BRCA gene muta-tion status can impact treatment decisions, so genetic testingshould be considered for any breast cancer patient who isreasonably likely to carry a mutation. In general, this

includes any breast cancer diagnosed at or before the ageof 45 years, triple-negative breast cancer diagnosed beforeage 60 years, or later onset breast cancer when there is asignificant family history of breast cancer, ovarian cancer, ormale breast cancer. The Agency of Healthcare Research andQuality (AHRQ) is currently developing a clinical supporttool to help physicians identify Hereditary Breast and Ovar-ian Cancer (HBOC) patients (DEcIDE Project). This web-based tool, called Cancer in the Family, will permit patientsto enter a cancer family history online and will then sum-marize their risk of carrying a mutation. Gene mutationprediction models such as BRCAPRO [40], BOADICEA[41], and Tyrer-Cusick [42] can be used as well. CancerGeneis a widely used desktop program that uses BRCAPRO toestimate mutation probabilities and cancer risks [43]. Modelprobabilities, including the probability of developing contra-lateral breast cancer, are adjusted according to BRCA genemutation status and oophorectomy.

Genetic Testing Guidelines and Reimbursement

Complete BRCA1/2 gene sequencing is quite expensive, soit is often the third-party payor who determines whethergenetic testing can be performed or not. Reimbursementpolicies are usually based on published genetic testingguidelines. The National Comprehensive Cancer Network(NCCN) publishes annual guidelines for screening patientsfor hereditary breast cancer (Table 1) as well as managementrecommendations for mutation-positive patients [44•].These guidelines address not only HBOC but also CowdenSyndrome and Li Fraumeni syndrome. Many insurers ac-cept these guidelines in their determinations of medicalnecessity. Medicare currently reimburses for BRCA genemutation testing in breast cancer patients diagnosed beforethe age of 45 years without a family history or in thosediagnosed at any age with more than two close bloodrelatives with breast and/or epithelial ovarian/fallopian tube/peritoneal cancer. Some state Medicaid plans also coverBRCA gene testing, but the reimbursement policies areunique to each state.

Many private insurers have established their own guide-lines for reimbursing genetic testing and some have exclud-ed it all together. A recent study analyzed the coveragepolicy differences between insurance companies, federalprograms, and state agencies and found significant differ-ences [45]. The policies ranged from BRCA gene testing notbeing a covered benefit at all, to other plans with detailedeligibility criteria including testing those individuals affectedwith cancer and those with just a strong family history. Ingeneral, government and private insurers are more likely tocover the costs of genetic testing for a breast cancer patientthan an unaffected woman. The cost of genetic testing and

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the lack of uniform reimbursement policies exclude manyindividuals who need genetic testing for treatment planning.Myriad Genetics, Inc., the primary provider of BRCA1/2gene testing services in the United States, does providegenetic testing at no charge for eligible uninsured individu-als making less than 200% of the United States Departmentof Health and Human Services Poverty Guidelines (ie, cur-rently $21,780 for households of one person). Nevertheless,cancer genetic counseling and testing remains a significantsource of health care disparity for the uninsured andunderinsured.

The Patient Protection and Affordable Care Act of 2010will affect coverage for BRCA gene testing and geneticcounseling. This new law prohibits a co-pay for preventivemedical services approved by the US Preventive ServicesTask Force (USPSTF). The USPSTF recommends thatwomen with a family history suggesting a deleterious mu-tation in the BRCA1 or BRCA2 gene be referred for geneticcounseling and evaluation for BRCA gene testing [46].Although this new law will help eliminate the financialbarrier for those seeking genetic counseling, BRCA genetictesting will still be considered a diagnostic service, leavingmany patients responsible for a substantial share of the costuntil their deductibles are met.

Genetic Counseling

Community-based genetic testing for HBOC, without formalgenetic counseling, is becoming more common. Consequently,a patient may present to your practice with a genetic test result

and little understanding of its implications. Explaining thecancer risks associated with a given test result is only onefunction of the professional genetic counselor. Genetic counse-lors can also direct patients to a specialist able to manage therelevant risks and facilitate contact with family members in aneffort to identify mutation carriers before they develop cancer.Competent genetic counseling is particularly essential when thetest result is negative or equivocal. If there is no positive test inthe family, other hereditary breast cancer syndromes must beconsidered such as Cowden syndrome or Li Fraumeni syn-drome. It must also be recognized that standard BRCA genetesting will miss large genomic deletions and rearrangements.These important mutations can be identified by BRCAnalysisRearrangement Testing (BART), but this type of testing is notroutinely performed for all patients. This may be particularlyrelevant to Hispanic and Near Eastern/Middle Eastern patientswho aremore likely to carry thesemutations thanwhite patients(personal communication, Myriad Genetics, July 2011).

Sometimes, extensive genetic analysis in an apparentlyclassic HBOC family fails to identify a deleterious mutationor identifies a variant of uncertain clinical significance.Individuals from these families need to be managed asthough they are mutation carriers. Some have suggested thatfamilies with a 30% probability of carrying a BRCA genemutation but no identifiable mutation should be managed asHBOC families [47].

Genetic Counselors

Practice guidelines for cancer genetic counseling have beenpublished by the National Society of Genetic Counselors

Table 1 Recommended guidelines for referral for genetic counseling and testing for hereditary breast and ovarian cancer syndrome

NCCN Medicare

Individual from a family with a known deleterious mutation in BRCA1/BRCA2 Yes No

BC ≤45 y Yes Yes

BC ≤50 y with ≥1 close blood relative with BC ≤50 y and/or ≥1 close relative with OC Yes Yes

Two BC primaries and ≥1 close relative with BC <50 y and/or ≥1 close relative with OC No Yes

2 breast primaries, when first BC occurred prior to age 50 y Yes Yes

BC <60 y with triple negative Yes No

BC <50 y with a limited family history Yes No

BC at any age, with ≥2 close relatives with BC or OC at any age Yes Yes

BC with close male relative with BC Yes Yes

BC and OV at any age Yes No

BC any age, and ethnicity associated with higher mutation frequency (Ashkenazi Jewish) Yes Yes

OC any age Yes Yes

Male BC Yes Yes

BC and/or OC at any age with ≥2 close relatives with BC, OC, and/or pancreatic cancer at any age Yes No

Pancreatic cancer any and age with ≥2 close relatives with BC, OC, and/or pancreatic cancer at any age Yes No

BC breast cancer (including ductal carcinoma in situ), NCCN National Comprehensive Cancer Network OC ovarian/fallopian tube/primaryperitoneal cancer

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[48]. In addition, in 2012 the American College of SurgeonsCommission on Cancer Accreditation program added a newstandard on Risk Assessment and Genetic Testing (http://www.facs.org/cancerprogram/index.html). This new stan-dard requires that cancer risk assessment, genetic counsel-ing, and genetic testing services be provided to patientseither on site or by referral, by a qualified genetic profes-sional. These new standards define the qualification of thegenetic professional and the elements involved in the pre-and post-test counseling. It is estimated that 80% of newlydiagnosed cancer patients are being treated in Commissionon Cancer Accredited Cancer programs. The NationalAccreditation Program for Breast Centers (NAPBC),which accredits approximately 200 breast centers in theUnited States, also has standards on cancer risk assess-ment, genetic counseling and genetic testing services(http://www.napbc-breast.org).

Timing of Genetic Counseling and Testing

Because a patient’s mutation status may affect the choice ofchemotherapy as well as surgical decisions, the optimal timeto offer genetic testing is prior to the initiation of anytherapy [49]. BRCA gene testing is most easily incorporatedinto the initial evaluation of new breast cancer patients incenters that are able to offer immediate or same-day cancergenetic counseling appointments. This resource is not avail-able in all centers. It is important to establish processes forinitiating rapid genetic counseling referrals for newly diag-nosed breast cancer patients. This may require the use ofcommercial telephone genetic counseling services that areavailable on demand.

Psychosocial Aspects of Preoperative GeneticCounseling

Testing a patient for a hereditary predisposition to cancer ismore involved than simply ordering a blood test. In obtaininginformed consent for the testing, the clinician or genetic coun-selor must address not only the clinical aspects of the test, butalso the psychological implications. The psychological impli-cations may be different when offering testing to a newlydiagnosed breast cancer patient as compared to the unaffectedpatient who has experienced cancer only through family mem-bers. After genetic counseling, women with a cancer diagnosishave been found to be more distressed compared to unaffectedwomen [50]. Newly diagnosed patients may focus on imme-diate treatment planning, information that is not usually themain focus of a cancer genetic counseling session [51].

In addition, there may be concerns that waiting for a testresult before starting therapy or providing one more piece of

bad news would increase patient anxiety. In the first case,turn around times for BRCA gene testing have steadilydecreased in recent years and now average 10 to 14 days.In the second case, one study found that if rapid breastcancer gene testing were to become available, a high pro-portion of patients would opt for immediate testing [52]. Atthe time this study was published (2005), the turnaroundtime for BRCA gene testing was 3 weeks, so using genetictesting for surgical decisions was not routinely done. Thissame study found that patients that were extremely anxiousabout their new cancer diagnosis were more likely to waitfor genetic testing results to plan their treatment. Anotherstudy evaluated patient satisfaction with the timing of theprovider recommendation for cancer genetic counselingeither before or after surgery and found no difference insatisfaction [53]. These results suggest that pre-treatmentgenetic testing is acceptable to newly diagnosed breastcancer patients.

Genetic Testing and Anxiety

Anxiety and depression related to genetic counseling andtesting has been a hotbed of research activity for severalyears. The general consensus, based on objective data, isthat genetic testing does not have an adverse effect on longterm psychological outcome [54, 55]. One study found thatpatients that attended a cancer genetic counseling sessiondid not suffer more anxiety or depression compared to othercancer-related groups [56]. Another study looked at thelong-term impact on psychological distress in 279 women6 months after testing [57] and found that patients whoreceived positive results did not exhibit increased psycho-logical risk whereas patients receiving a negative test resulthad psychological benefits. Overall, the benefits of preop-erative genetic counseling in the majority of patients willoutweigh any perceived or actual psychological stress oranxiety related to testing.

Reasons Patients Decline Genetic Counseling or Testing

Some patients will decline genetic counseling and testingirrespective of the timing of the recommendation. It isinstructive to understand why these patients decline genetictesting [58]. One study evaluated 231 patients who had notyet started definitive breast cancer treatment to identifyfactors associated with specific testing decisions [52]. Inthis study, 9% of patients declined the initial referral togenetic counseling and 15% declined after the geneticcounseling interview. Overall, 76% of patients underwentgenetic testing. Some patients declined the initial offer ofgenetic counseling and testing because they did not see thetesting as relevant and/or they did not perceive their risk as

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high [59]. In some cases, the newly diagnosed patient isgiven multiple medical appointments in a short timeframe,and some feel that they cannot accommodate yet anotherappointment. Patients who are emotionally overwhelmedare more likely to decline genetic counseling and testing.However, one of the strongest predicators of a patient’swillingness to pursue genetic counseling and testing is thephysician’s recommendation [53]. It is critical that physi-cians understand the implications of BRCA gene mutationstatus in newly diagnosed breast cancer patients and clearlycommunicate this information to their patients.

Patients also need to understand that coming to a geneticcounseling appointment does not mean that they must havegenetic testing. The role of the genetic specialist is to helpthe patient understand the benefits as well as the limitationsof the testing. When a patient declines genetic testing afterthe counseling session, the reasons for the refusal are usu-ally different than the reasons given for declining the initialreferral. Common reasons for declining an indicated genetictest include out-of-pocket expense, concerns about health,life, and disability insurance, job discrimination, time awayfrom work or family, emotional impact of the testing, andconcerns that less screening or treatment will be done if noBRCA gene mutation is identified.

Conclusions

BRCA gene mutation status is emerging as an importantprognostic and predictive factor in breast cancer. This infor-mation can directly impact decisions about primary surgery,radiation therapy, and chemotherapy. Preoperative genetictesting can be performed with short turnaround times anddoes not increase patient anxiety. It is essential to incorpo-rate a professional genetic counselor into the managementteam early in the evaluation of breast cancer patients whomay carry a mutation.

Disclosure D. Euhus: none. L. Robinson is an unpaid board memberof the National Society of Genetic Counselors and has been a consultant(regarding colon cancer) for Myriad Genetics, Inc.

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