Science-Research Paper

EPIDEMIOLOGY

Rates of BRCA1/2 mutation testing among young survivors of breast cancer

Kenneth L. Kehl1 • Chan Shen2 • Jennifer K. Litton3 •

Banu Arun3 • Sharon H. Giordano2

Received: 1 December 2015 / Accepted: 8 December 2015 / Published online: 26 December 2015

� Springer Science+Business Media New York 2015

Abstract Guidelines in the United States recommend

consideration of testing for mutations in the BRCA1 and

BRCA2 genes for women diagnosed with breast cancer

under age 45. Identification of mutations among survivors

has implications for secondary prevention and familial risk

reduction. Although only 10 % of breast cancers are

diagnosed under age 45, there are approximately 2.8 mil-

lion breast cancer survivors in the United States, such that

the young survivor population likely numbers in the hun-

dreds of thousands. However, little is known about genetic

testing rates in this population. We assessed trends in

BRCA1/2 testing among breast cancer survivors who were

under age 45 at diagnosis and were treated from 2005 to

2012. Using insurance claims from a national database

(MarketScan), we identified incident breast cancer cases

among (1) women aged B40 and (2) women aged 41–45.

We measured BRCA1/2 testing using Kaplan–Meier

analysis and Cox proportional hazards models. Among

26,985 patients analyzed, BRCA1/2 testing rates increased

with each year of diagnosis from 2005 to 2012

(P \ 0.001). However, among women treated in earlier

years, testing rates did not approach those of patients

treated later, even after extended follow-up (median time

from surgery to testing among patients treated in 2005, not

reached; median time to testing among patients treated in

2012, 0.2 months for women aged B40 and 1.0 month for

women aged 41–45). Women aged 41–45 had lower rates

than women aged B40 throughout the analysis period

(P \ 0.001 for each year). BRCA1/2 testing rates among young women with incident breast cancer increased sub-

stantially in the last decade. However, most survivors

treated in earlier years have never been tested. Our results

demonstrate a need to better incorporate genetic counseling

into survivorship and primary care for this population.

Keywords BRCA1 � BRCA2 � Breast cancer genetics � Health services research

Introduction

Mutations in the BRCA1 and BRCA2 genes are associated

with under 10 % of breast cancer cases [1, 2]. However,

germline mutations in BRCA1 or BRCA2 confer a sub-

stantially increased risk of breast cancer, with a cumulative

incidence by age 70 of 44–78 % among BRCA1 mutation

carriers and 31–56 % among BRCA2 mutation carriers

[1, 3].

In 2001, the National Comprehensive Cancer Network

(NCCN) recommended consideration of genetic testing for

patients with a history of breast cancer diagnosed at age

B40 and for patients with clinical or family histories

otherwise suggestive of the hereditary breast and ovarian

cancer syndrome [4]. By 2005, consideration of testing was

additionally recommended for patients between ages 40

and 50, if deemed clinically appropriate [5]. The 2009

Electronic supplementary material The online version of this article (doi:10.1007/s10549-015-3658-y) contains supplementary material, which is available to authorized users.

& Kenneth L. Kehl [email protected]

1 Division of Cancer Medicine, University of Texas MD

Anderson Cancer Center, 1515 Holcombe Blvd, Unit 463,

Houston, TX 77030, USA

2 Department of Health Services Research, University of Texas

MD Anderson Cancer Center, Houston, TX, USA

3 Department of Breast Medical Oncology, University of Texas

MD Anderson Cancer Center, Houston, TX, USA

123

Breast Cancer Res Treat (2016) 155:165–173

DOI 10.1007/s10549-015-3658-y

guidelines increased the upper limit for age at diagnosis for

which testing should be generally considered from 40 to

45 years [6]. Other testing criteria for women include triple

negative breast cancer diagnosed at age B60, any epithelial

ovarian cancer, and pancreatic cancer in the setting of a

concerning family history [7]. In one study of patients with

incident breast cancer diagnosed from 2004 to 2007, 30 %

of women aged B40 had BRCA1/2 testing, and black and

Hispanic women were less likely to have testing than white

women [8]. However, testing rates began to increase sub-

stantially for women diagnosed at the end of that study

period, and it is not known to what degree that trend has

impacted survivors with more remote diagnoses.

There are currently 2.8 million survivors of breast can-

cer living in the United States [9], so although just 10 % of

cases of breast cancer are diagnosed at age B45 [10], the

number of survivors from that age group is likely in the

hundreds of thousands. Within the oncology community,

there is increasing interest in genetic testing and especially

in novel gene panel testing in breast cancer [11–14], but

long-term survivors of breast cancer have fewer visits to an

oncologist with each passing year [15]. Consideration of

even basic, standard-of-care genetic testing may therefore

not be routinely incorporated into the care of young sur-

vivors who were not tested at the time of diagnosis. Nev-

ertheless, identification of BRCA1 and BRCA2 mutations

within the survivor population has implications for pre-

vention of ovarian cancer and a second primary breast

cancer [16], as well as for genetic testing and risk reduction

within families.

In this study, we used insurance claims data to assess

rates of BRCA1/2 testing within a cohort of privately

insured young women with incident breast cancer treated in

the United States from 2005 to 2012. Since the 2009

NCCN guidelines were the first to explicitly recommend

consideration of testing for all women diagnosed under age

45, we separately analyzed women diagnosed at age B40

and women diagnosed at age 41 to 45. Our specific aim was

to assess for differences in genetic testing rates among

survivors according to year of diagnosis.

Methods

We identified patients with incident breast cancer diag-

nosed from 2005 to 2012 using the MarketScan database

[17]. We specifically analyzed rates of BRCA1/2 testing

among (1) women aged B40 at diagnosis and (2) women

aged 41–45 at diagnosis.

MarketScan [17] is a proprietary database consisting of

a convenience sample of paid medical claims for patients

with employment-based health insurance. This dataset

contains health insurance claims data for individuals in the

United States with primary or Medicare supplemental

coverage. The data are de-identified and meet Health

Insurance Portability and Accountability (HIPAA) confi-

dentiality requirements [17, 18]. For this analysis, we used

data from the Commercial Claims and Encounters and the

Medicare Supplemental and Coordination of Benefits

databases. We applied a modified version of the Nattinger

algorithm [19–21] to identify incident breast cancer cases.

Briefly, potential cases were identified based upon a breast

cancer ICD-9 code (174.x, malignant neoplasm of the

female breast). The algorithm further identified patients

who additionally had a procedure code for mastectomy,

lumpectomy, or axillary lymph node dissection. Patients

who met these criteria were included if they had at least

two outpatient claims on different dates with a primary

diagnosis of breast cancer, as well as either (1) a mastec-

tomy claim or (2) a lumpectomy or partial mastectomy

claim followed by at least one radiation therapy claim.

They could also be included if they had a surgical claim

plus at least two claims with a primary breast cancer

diagnosis but did not have both a claim for another type of

cancer and a claim for secondary cancer of the breast (ICD-

9 codes 198.81 or 198.2). Patients with a claim under a

breast cancer diagnosis or for a breast cancer procedure

within the preceding 3 years, indicating prevalent rather

than incident cases, were excluded. To capture claims for

BRCA1/2 testing that occurred close in time to the diag-

nosis of the index cancer, we included patients diagnosed

from 2005 to 2012 who had continuous coverage through

6 months prior to the month of their index cancer-directed

procedure and during the month of that procedure. We did

not otherwise require a continuous coverage period after

the index cancer-directed procedure, but rather censored

patients in our analyses on the date they no longer had

continuous documented coverage. Patients with docu-

mented BRCA testing claims prior to 6 months before

diagnosis were excluded. The year of diagnosis was

defined as the year in which there was a claim for the index

breast cancer surgery.

We identified BRCA1/2 testing claims using mutation-

specific HCPCS procedure codes S1818–S1823, as previ-

ously described [8]. These codes were discontinued in

2012, and Medicare then introduced new specific HCPCS

codes 81211–81217 for BRCA testing [22, 23]; we also

included claims filed under the new codes. A primary aim

of our analysis was to identify potential underuse of testing,

so we sought to capture as many potential BRCA mutation

testing claims as possible. In our primary analysis, we

therefore also included claims filed under stackable CPT

codes 83890–83909, 83912, 83914, or 88271, which until

2012 could be used to bill for molecular biological tech-

niques that might have been used for BRCA1/2 testing.

Since these codes were not specific for BRCA testing, we

166 Breast Cancer Res Treat (2016) 155:165–173

123

included them only when filed under an ICD-9 code for a

personal history of breast cancer (174.x–175.x, 233.0,

V10.03), genetic counseling and testing (V26.3x), or other

genetic screening (V82.79). We also conducted a sensi-

tivity analysis that included only the BRCA1/2 mutation-

specific procedure codes. Since HCPCS procedure codes

S1818–S1823 would not have been covered by Medicare,

and Medicare patients may therefore not have had such

claims submitted, we performed a second sensitivity

analysis excluding patients with Medicare supplemental

coverage.

We assessed rates of BRCA1/2 mutation testing, and

timing of testing, using Kaplan–Meier analyses. To capture

BRCA1/2 testing claims that followed identification of

cancer but predated cancer surgery, we defined the index

date for these analyses as 6 months (180 days) prior to

surgery. Patients were censored on the date they were no

longer included in the database due to changes in insurance

coverage or at the end of the follow-up period (December

31, 2013). Time to testing was compared among years of

diagnosis within patient cohorts via the log-rank test.

Confidence bands in our figures were generated via the

Hall–Wellner method [24]. We conducted multivariable

analyses using Cox proportional hazards models. Two-

sided P values less than 0.05 were considered statistically

significant. Analyses were performed using SAS software,

version 9.4 (SAS Institute, Cary, NC).

Results

We identified 35,388 patients with incident breast cancer

(15,149 women aged B40 and 20,239 women aged 41–45)

who had surgery from 2005 to 2012. Of those patients, we

excluded 3584 women aged B40 and 4223 women aged

41–45 who did not have continuous documented insurance

coverage for the month of their index breast cancer surgery

and the 180 days prior to surgery. We also excluded 365

women aged B40 and 231 women aged 41–45 who had

documentation of BRCA1/2 testing prior to a 180 day

period before surgery. Our analysis cohort therefore

included 26,985 patients (Table 1). Continuous insurance

coverage data for patients treated in each year are listed in

Supplemental Table 1.

Patients treated in later years were more likely to have

genetic testing; nevertheless, despite these increases,

patients treated in earlier years had lower plateaus in their

testing rates with time (Table 2; Fig. 1; log-rank P \ 0.001 for women aged B40 at diagnosis and for women aged

41–45 at diagnosis). Among women aged B40 treated in

2012, 72.9 % (95 % CI 70.7–75.1 %) had genetic testing

within 1 year after breast cancer surgery, and the median

time from surgery to testing was 0.2 months. Similarly,

among women aged 41–45 treated in 2012, 65.3 % (95 %

CI 63.3–67.3 %) had genetic testing by 1 year after sur-

gery, and the median time from surgery to testing was

1.0 month. However, among women treated in 2005 and

followed over time, less than half had testing as of

December 31, 2013 (median not reached for women aged

B40 at diagnosis or women aged 41–45 at diagnosis;

Table 2). Among women aged B40 treated in 2005, 4.9 %

(95 % CI 3.7–6.5 %) had a claim for genetic testing by the

date of surgery, but among women aged B40 treated in

2012, 47.5 % (95 % CI 45.1–49.9 %) had a testing claim

by their surgery date.

In a multivariable Cox proportional hazards model,

women aged B40 consistently had a higher likelihood of

testing than women aged 41–45 (P \ 0.001 for the contrast between the cohorts in each year from 2005 to 2012).

There was slight variation in testing rates according to

geographic region and insurance plan type (Table 3).

In a sensitivity analysis restricted to claims specific to

BRCA 1/2 mutation testing (excluding non-specific genetic

testing claims for molecular techniques), estimated testing

rates were lower, but the patterns of change over time were

similar (Supplemental Table 2; Supplemental Fig. 1). We

also conducted a second sensitivity analysis excluding

patients with Medicare supplemental coverage, since

Medicare would not have reimbursed HCPCS ‘S’ codes

under which most of the BRCA1/2 mutation testing claims

were billed. The patterns of change remained similar

(Supplemental Table 3; Supplemental Fig. 2).

Discussion

In a cohort of young women with employer-based or

Medicare supplemental insurance and breast cancer treated

from 2005 to 2012, we found that a large proportion of

young breast cancer survivors have not undergone testing

for mutations in the BRCA1 and BRCA2 genes. Rates of

testing increased substantially for patients treated in later

years, but testing rates for patients treated in earlier years

never approached those of patients treated later, even after

extended follow-up. In the United States, approximately

7 % of cases of breast cancer occur before the age 40 [25],

and approximately 10 % of cases occur before the age 45

[10]. During our study period alone, there were therefore

approximately 192,000 cases of breast cancer in this age

group. We found that less than half of patients diagnosed in

2005 had genetic testing by the end of 2013. At a time

when there is increasing interest in issues around expanded

panel genetic testing for newly diagnosed patients with

breast cancer [11–14], our results indicate that there is a

substantial population of survivors who have never

undergone established, standard-of-care genetic testing.

Breast Cancer Res Treat (2016) 155:165–173 167

123

We found an increase in testing rates with each suc-

cessive year at diagnosis, during a period when genetic

testing was becoming more readily available, likely indi-

cating that most young patients with breast cancer who are

offered genetic testing are interested in pursuing it. The

lower plateau in testing rates among young women diag-

nosed in earlier years, even after extended follow-up, is

therefore especially notable. Although some studies indi-

cate that patients with BRCA1/2-associated breast cancers

have a worse prognosis than those with sporadic disease

[26, 27], others have demonstrated that the two groups

have similar outcomes [28–32]. Furthermore, the large

majority of patients diagnosed with breast cancer will be

long-term survivors [33]. Some of these survivors, such as

the cohort of women in our analysis who were aged 41–45

at diagnosis, would meet current criteria for genetic testing

but may not have met criteria when they were diagnosed.

Other survivors may have been diagnosed when genetic

counseling and testing were less widely available or prior

to the protections extended by the Genetic Information

Nondiscrimination Act of 2008, which prohibited dis-

crimination in the workplace or health insurance market-

place on the basis of a genetic predisposition to disease.

Our results indicate that providers should consider offering

genetic testing to this population, given the possibility that

doing so may further mitigate cancer risks, both for

Table 1 Patient characteristics Women aged B40 N (%) Women aged 41–45 N (%)

Total 11,200 (100) 15,785 (100)

Age at diagnosis

B25 210 (2)

26–30 831 (7)

31–35 2776 (25)

36–40 7383 (66)

41–45 15,785 (100)

Index surgery claim

Lumpectomy 5967 (53) 10,177 (64)

Mastectomy 4461 (40) 4878 (31)

Other* 772 (7) 730 (5)

Insurance plan type �

PPO 6887 (61) 9673 (61)

CDHP 411 (4) 600 (4)

Comprehensive 145 (1) 282 (2)

EPO 178 (2) 250 (2)

HDHP 213 (2) 274 (2)

HMO 1828 (16) 2507 (16)

POS 943 (8) 1300 (8)

POS with capitation 104 (0.9) 142 (0.9)

Missing/unknown 491 (4) 757 (5)

Region

Northeast 1729 (15) 2673 (17)

South central 2579 (23) 3677 (23)

South 4774 (43) 6455 (41)

West 1868 (17) 2642 (17)

Missing/unknown 250 (2) 338 (2)

* Other surgery type includes patients whose index surgery claim was for regional node dissection only or

whose index claim contained both a mastectomy and a lumpectomy procedure code �

Insurance plan type: PPO preferred provider organization; CDHP consumer-driven health plan (PPO

combined with a health reimbursement arrangement); comprehensive (coverage handled by one policy with

deductible and coinsurance, no incentive for use of particular providers); EPO exclusive provider orga-

nization (all care managed by a primary care physician with referrals required, payment non-capitated);

HDHP high deductible health plan combined with health savings account; HMO health maintenance

organization; POS point-of-service (primary care physician manages care; patients incentivized to use

particular providers)

168 Breast Cancer Res Treat (2016) 155:165–173

123

T a b le

2 R a te s o f B R C A 1 /2

m u ta ti o n te st in g

Y e a r o f b re a st su rg e ry

N O u tc o m e s o f K a p la n – M e ie r a n a ly si s (%

) K a p la n – M e ie r e st im

a te s o f B R C A 1 /2

te st in g ra te s*

C e n so re d b e fo re

1 2 /3 1 /1 3

F o ll o w -u p

to 1 2 /3 1 /1 3

B R C A 1 /2

te st in g

M e d ia n ti m e to

te st in g

(m o n th s a ft e r su rg e ry )

B y su rg e ry

d a te

%

(9 5 %

C I) �

B y 1 y e a r a ft e r

su rg e ry

% (9 5 %

C I) �

B y 5 y e a rs

a ft e r

su rg e ry

% (9 5 %

C I) �

2 0 0 5

W o m e n a g e d 4 0 a n d u n d e r

9 1 4

6 3 .0

1 0 .9

2 6 .0

N o t re a c h e d

4 .9

(3 .7 – 6 .5 )

1 9 .6

(1 7 .0 – 2 2 .5 )

3 5 .3

(3 1 .1 – 3 9 .9 )

W o m e n a g e d 4 1 – 4 5

1 3 7 5

6 3 .6

1 5 .9

2 0 .5

N o t re a c h e d

2 .2

(1 .5 – 3 .1 )

1 3 .1

(1 1 .4 – 1 5 .2 )

2 5 .0

(2 2 .1 – 2 8 .2 )

2 0 0 6

W o m e n a g e d 4 0 a n d u n d e r

8 8 8

4 5 .3

1 1 .6

4 3 .1

6 6 .4

6 .6

(5 .2 – 8 .5 )

3 2 .9

(2 9 .9 – 3 6 .3 )

4 8 .3

(4 4 .5 – 5 2 .3 )

W o m e n a g e d 4 1 – 4 5

1 3 2 3

5 4 .7

1 7 .6

2 7 .7

N o t re a c h e d

4 .8

(3 .7 – 6 .1 )

1 9 .2

(1 7 .1 – 2 1 .5 )

3 0 .6

(2 7 .8 – 3 3 .7 )

2 0 0 7

W o m e n a g e d 4 0 a n d u n d e r

1 1 4 1

4 0 .2

1 1 .2

4 8 .6

4 0 .6

1 2 .1

(1 0 .3 – 1 4 .1 )

3 9 .8

(3 6 .9 – 4 2 .7 )

5 3 .1

(4 9 .8 – 5 6 .5 )

W o m e n a g e d 4 1 – 4 5

1 6 4 8

4 8 .1

1 6 .0

3 5 .9

N o t re a c h e d

7 .3

(6 .2 – 8 .7 )

2 6 .5

(2 4 .4 – 2 8 .8 )

4 1 .8

(3 9 .0 – 4 4 .7 )

2 0 0 8

W o m e n a g e d 4 0 a n d u n d e r

1 5 4 4

3 5 .7

1 0 .3

5 4 .0

1 3 .9

1 9 .5

(1 7 .7 – 2 1 .6 )

4 8 .5

(4 6 .0 – 5 1 .1 )

6 1 .2

(5 8 .2 – 6 4 .2 )

W o m e n a g e d 4 1 – 4 5

2 1 6 7

4 2 .4

1 5 .4

4 2 .2

6 7 .7

1 1 .4

(1 0 .1 – 1 2 .8 )

3 5 .4

(3 3 .4 – 3 7 .5 )

4 8 .4

(4 5 .9 – 5 1 .0 )

2 0 0 9

W o m e n a g e d 4 0 a n d u n d e r

1 7 6 7

3 0 .2

1 0 .3

5 9 .5

4 .5

2 8 .6

(2 6 .6 – 3 0 .8 )

5 7 .3

(5 4 .9 – 5 9 .7 )

N /A

W o m e n a g e d 4 1 – 4 5

2 5 7 1

3 7 .9

1 6 .0

4 6 .2

4 2 .1

1 7 .2

(1 5 .8 – 1 8 .7 )

4 3 .1

(4 1 .1 – 4 5 .1 )

N /A

2 0 1 0

W o m e n a g e d 4 0 a n d u n d e r

1 7 0 0

2 3 .3

1 2 .4

6 4 .4

2 .1

3 4 .1

(3 1 .9 – 3 6 .4 )

6 1 .5

(5 9 .2 – 6 3 .9 )

N /A

W o m e n a g e d 4 1 – 4 5

2 1 5 8

2 8 .0

1 9 .1

5 2 .8

1 5 .0

2 2 .7

(2 1 .0 – 2 4 .5 )

4 8 .4

(4 6 .2 – 5 0 .5 )

N /A

2 0 1 1

W o m e n a g e d 4 0 a n d u n d e r

1 5 7 2

1 8 .1

1 3 .8

6 8 .1

0 .8

3 8 .7

(3 6 .3 – 4 1 .1 )

6 6 .4

(6 4 .0 – 6 8 .7 )

N /A

W o m e n a g e d 4 1 – 4 5

2 2 3 4

2 2 .7

1 8 .8

5 8 .6

4 .5

2 9 .7

(2 7 .9 – 3 1 .7 )

5 6 .1

(5 4 .1 – 5 8 .3 )

N /A

2 0 1 2

W o m e n a g e d 4 0 a n d u n d e r

1 6 7 4

1 2 .8

1 4 .2

7 3 .0

0 .2

4 7 .5

(4 5 .1 – 4 9 .9 )

7 2 .9

(7 0 .7 – 7 5 .1 )

N /A

W o m e n a g e d 4 1 – 4 5

2 3 0 9

1 5 .2

2 0 .0

6 4 .8

1 .0

3 8 .3

(3 6 .3 – 4 0 .3 )

6 5 .3

(6 3 .3 – 6 7 .3 )

N /A

* T h e b e g in n in g o f th e K a p la n – M e ie r a sc e rt a in m e n t p e ri o d w a s d e fi n e d a s 6 m o n th s b e fo re

th e d a te

o f b re a st

c a n c e r su rg e ry

� 9 5 %

C I 9 5 %

p o in tw is e c o n fi d e n c e in te rv a l fo r th e K a p la n – M e ie r e st im

a te

Breast Cancer Res Treat (2016) 155:165–173 169

123

patients and their families [16]. Information regarding

hereditary risk factors and genetic testing results is a rec-

ommended component of survivorship care planning for

current patients [34]. However, patients with remote

diagnoses may be unaware of advances in genetic testing.

Optimizing this process will require engagement of

Fig. 1 Cumulative rates of BRCA1/2 testing claims. Each

graph contains Kaplan–Meier

failure curves, where events

were defined as BRCA1/2

testing claims. The year of

diagnosis was defined as the

year in which breast cancer

surgery occurred; the

observation period began

180 days before the date of

breast cancer surgery. Patients

were censored on the date they

no longer had continuous

insurance coverage recorded

within the MarketScan database.

The shaded areas represent

95 % Hall–Wellner confidence

bands for each curve

170 Breast Cancer Res Treat (2016) 155:165–173

123

primary care providers, since with more time since diag-

nosis, long-term survivors of breast cancer have more visits

with their primary care physicians and fewer visits with

their oncologists [15].

Strengths of our analysis included its basis in a large

database of privately insured patients, which provided a

nationwide sample [17] with which to assess rates of genetic

testing in young women with breast cancer. Nevertheless,

there are limitations. We studied subgroups of breast cancer

patients with indications for genetic testing based on age

alone, who could therefore be identified from insurance

claims data using a previously validated algorithm [19–21].

This is not a complete list of indications for BRCA1/2

testing; for example, individuals are also eligible if they

have consistent family history patterns, ovarian cancer, or

triple negative breast cancer diagnosed at age B60, or if they

are male [7]. We also studied a privately insured population,

which may limit the generalizability of our results. Still,

rates of genetic testing were likely higher in the population

we studied than in patients who were uninsured or covered

by Medicaid or Medicare without supplemental coverage, or

who had less obvious or more recently identified indications

for testing. In that case, the rates of genetic testing we

ascertained may, in fact, represent an upper limit relative to

those in the general population. This would further reinforce

the need to consider genetic testing for survivors to whom it

has not previously been offered.

In addition, follow-up in our analysis was based on

continuous insurance coverage within a plan included in

the MarketScan database. Given a median length of follow-

up of three to 4 years, many patients diagnosed in earlier

years were censored. However, the upper quartile of length

of follow-up extended to 7–8 years for patients diagnosed

in 2005–2006, which still allowed us to assess rates of

genetic testing over an extended period of time for patients

with long-term data. Although our data cannot inform this

question directly, there is no obvious reason to suspect that

censoring would lead to a systematic underestimation of

BRCA1/2 testing rates. Indeed, patients who were censored

may actually have been less likely to have BRCA1/2

testing due to competing health risks. In that case, our low

measured testing rates for patients diagnosed in earlier

years might again represent an upper limit estimate of

actual population rates among cancer survivors.

This analysis was based on paid insurance claims, and

we therefore could not assess how often providers dis-

cussed the possibility of genetic testing with these patients

or how often patients were referred for genetic counseling.

We also could not assess how often patients considered

genetic testing but decided not to have it done, chose to pay

privately for testing rather than submit an insurance claim,

or had a claim for genetic testing denied without subse-

quently submitting a claim that was paid.

Table 3 Multivariable Cox proportional hazards model for BRCA1/2 testing

HR (95 % CI) P

Diagnosis year/cohort \0.001 2005

Women aged B40 Reference

Women aged 41–45 0.71 (0.60–0.84)

2006

Women aged B40 1.70 (1.44–2.00)

Women aged 41–45 0.97 (0.82–1.14)

2007

Women aged B40 2.11 (1.81–2.46)

Women aged 41–45 1.39 (1.19–1.62)

2008

Women aged B40 2.71 (2.34–3.13)

Women aged 41–45 1.83 (1.59–2.12)

2009

Women aged B40 3.42 (2.97–3.94)

Women aged 41–45 2.23 (1.94–2.57)

2010

Women aged B40 4.03 (3.50–4.65)

Women aged 41–45 2.75 (2.39–3.17)

2011

Women aged B40 4.77 (4.14–5.50)

Women aged 41–45 3.48 (3.03–4.00)

2012

Women aged B40 6.05 (5.26–6.97)

Women aged 41–45 4.63 (4.03–5.33)

Insurance plan type � \0.001

PPO Reference

CDHP 1.14 (1.05–1.24)

Comprehensive 1.01 (0.87–1.17)

EPO 1.05 (0.93–1.19)

HDHP 1.26 (1.13–1.40)

HMO 0.86 (0.82–0.91)

POS 1.03 (0.97–1.10)

POS with capitation 1.17 (0.98–1.41)

Missing/unknown 0.90 (0.83–0.98)

Region \0.001 South Reference

Northeast 1.15 (1.09–1.21)

South central 1.18 (1.13–1.23)

West 1.06 (1.00–1.11)

Missing/unknown 1.18 (1.06–1.32)

The outcome was the first BRCA1/2 testing claim recorded, using a

Cox proportional hazards model that included the three independent

variables listed in this table � Insurance plan type: PPO preferred provider organization; CDHP

consumer-driven health plan (PPO combined with a health reim-

bursement arrangement); EPO exclusive provider organization (all

care managed by a primary care physician with referrals required,

payment non-capitated); HDHP high deductible health plan combined

with health savings account; HMO health maintenance organization;

POS point-of-service (primary care physician manages care; patients

incentivized to use particular providers)

Breast Cancer Res Treat (2016) 155:165–173 171

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Finally, our case-finding algorithm may not have cap-

tured all breast cancer patients who had metastatic disease

at diagnosis, and therefore did not undergo surgery [20].

However, only approximately 4 % of female patients with

breast cancer have distant metastatic disease at diagnosis

[35]. Furthermore, approximately half of patients diag-

nosed with stage IV disease undergo surgery for their

primary tumor [36] and may therefore have been captured

by our algorithm, so the proportion of patients excluded for

this reason was likely small.

In conclusion, within a cohort of young women treated

for breast cancer from 2005 to 2012, for whom current

guidelines recommend consideration of BRCA1/2 testing,

rates of testing increased with later years of diagnosis. Still,

survivors treated in earlier years and followed over time

never approached the testing rates of those diagnosed in

later years. There are approximately 2.8 million survivors

of breast cancer in the United States [9], and approximately

10 % of new cases are diagnosed at age B45 [10], such that

there are likely hundreds of thousands of current survivors

from this population. Our results point to a need to opti-

mize access to genetic counseling among eligible survivors

and to incorporate it into survivorship and primary care for

patients with a history of successful treatment for early-

stage disease. Further research should be conducted into

strategies for increasing awareness of advances in genetic

testing among cancer survivors and their physicians, and

into assessment of the clinical impact and cost of such

efforts.

Funding This work was supported by the Duncan Family Institute, the Baker Institute for Health and Biosciences, and the Cancer

Prevention Research Institute of Texas (Grant RP140020).

Compliance with ethical standards

Conflict of Interest Kenneth L. Kehl declares that he has no con- flict of interest. Chan Shen declares that she has no conflict of interest.

Jennifer K. Litton declares that she has no conflict of interest. Banu

Arun declares that she has no conflict of interest. Sharon H. Giordano

declares that she has no conflict of interest.

Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors. The

MarketScan insurance claims data were fully de-identified prior to

analysis, and the Institutional Review Board at the University of

Texas MD Anderson Cancer Center exempted this study from review.

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