A total of 5,712 women had a diagnosis of breast cancer during 1995–2014 of which 835 (14.6%) were tested for a BRCA mutation with documented results from BRCA testing (Myriad Laboratories, Inc.) The number of women undergoing BRCA testing increased from 2000–2014. When categorized by 5-year increments by year of diagnosis, 5.7% women were tested during 2000–2004, 17.1% were tested during 2005–2009, and 23.1% were tested during 2010–2014. Of the 835 patients with BRCA testing, 816 had valid charge data and were included in the study. There were 134 (16.4%) patients with a BRCAm mutation and 682 (83.6%) patients were BRCAwt. Within these groups, HER2 + tumors were observed in 15 (11.2%) and 127 (18.6%) patients; HER2- tumors were seen in 91 (67.9%) and 430 (63.0%) patients; and 28 (20.9%) BRCAm and 125 (18.3%) BRCAwt patients had other/unknown status (Fig. 1a).
With respect to initial treatment setting after breast cancer diagnosis, 553 (67.8%) patients received adjuvant therapy, 148 (18.1%) patients received neoadjuvant therapy, and 73 (8.9%) patients had surgical resection alone. There were 42 (5.1%) patients who presented with metastatic breast cancer at the time of diagnosis. Of the patients who received adjuvant, neoadjuvant and surgical resection at diagnosis, 58 (10.5%), 25 (16.9%), and 15 (20.5%) progressed to metastatic disease during the study period respectively. The median time to progression for these 98 patients was 3.5 years (± IQR 2.2–9.7 years). Thus, of the total 140 patients who had metastatic disease during the study period, 133 (16.3% of 816 patients) had valid charges (Fig. 1b).
Table 1 lists the demographic and clinical characteristics of these patients. Age at diagnosis was similar between BRCAm and BRCAwt (45.9 years vs. 47.1 years) patients; breast cancer stage at diagnosis was also similar between the two groups. BRCAm patients had significantly longer median follow-up times (62.4 [± 74.5] months vs. 46.6 [± 57.7] months, p = 0.0045), The BRCAm group had more triple negative breast cancer patients vs. BRCAwt group (28.4% vs. 11.9%). More BRCAm patients had grade 3 histological tumor grades and conversely, more BRCAwt patients had grade 2 histology (Grade 1: 52.2% vs. 32.0%; Grade 2: 38.1% vs. 45.0%).
Table 1
Demographic and Clinical Characteristics of the Study Sample
Variables | BRCAm (n = 134) | BRCAwt (n = 682) | BRCAm vs. BRCAwt p-value |
Demographic Characteristics | | | |
Age, Mean ± SD | 45.9 ± 9.4 | 47.1 ± 11.7 | 0.2575* |
Age, Median ± IQR | 45.0 ± 12.9 | 45.9 ± 14.7 | 0.3853† |
Ethnicity | | | |
Caucasian/ White | 116 (86.6%) | 598 (87.5%) | 0.9377‡ |
Non-White | 10 (7.5%) | 47 (6.9%) |
Unknown | 8 (6.0%) | 37 (5.4%) |
Plan Type | | | |
Commercial | 93 (69.4%) | 426 (62.5%) | 0.1324‡ |
Medicare | 6 (4.5%) | 60 (8.8%) |
Medicaid | 9 (6.7%) | 31 (4.6%) |
Other/Unknown | 26 (19.4%) | 165 (24.2%) |
Clinical Characteristics | | | |
Stage at diagnosis | | | |
I | 51 (38.1%) | 262 (38.4%) | 0.7387* |
II | 51 (38.1%) | 250 (36.7%) |
III | 16 (11.9%) | 107 (15.7%) |
IV | 9 (6.7%) | 34 (5.0%) |
Unknown | 7 (5.2%) | 29 (4.3%) |
Receptor status | | | |
ER+/PR+/HER2- | 53 (39.6%) | 349 (51.2%) | < 0.0001* |
ER+/PR+/HER 2+ | 7 (5.2%) | 87 (12.8%) |
TNBC | 38 (28.4%) | 81 (11.9%) |
ER-/PR-/HER2+ | 8 (6.0%) | 40 (5.9%) |
Other/Unknown | 28 (20.9%) | 125 (18.3%) |
Tumor histologic grade | | | |
1 | 7 (5.2%) | 115 (16.9%) | < 0.0001* |
2 | 51 (38.1%) | 307 (45.0%) |
3 | 70 (52.2%) | 218 (32.0%) |
Unknown | 6 (4.5%) | 42 (6.2%) |
SD – Standard Deviation; IQR – Interquartile Range; TNBC – Triple Negative Breast Cancer (ER-/PR-/HER2-) |
*T-Test |
†Wilcoxon Rank Sum Test |
‡Chi-Squared Test |
Comparison of health care cumulative charges between BRCAm and BRCAwt patients
Total mean (SD) breast cancer related charges were similar between BRCAm vs. BRCAwt patients, $86,689 ($75,937) vs. $85,843 $97,304, p = 0.19, respectively (Table 2) while all-cause charges were significantly higher for BRCAm patients ($145,066 [$117,462] vs. $119,119 [$122,169], p < 0.001; Fig. 2). Facility/technical charges accounted for 40.5% and 32.5% of the total breast cancer related charges for BRCAm and BRCAwt groups (Table 2). Pharmacy charges accounted for 40.8% and 49.4% of total breast cancer charges for BRCAm and BRCAwt groups (Table 2). Chemotherapy was received by 58% of patients and accounted for 23.9% of pharmacy charges for BRCAm patients; biologics were received by 16% of patients and accounted for 43.0% of pharmacy charges for BRCAwt patients. Physician/professional charges accounted for 18.7% and 18.1% of the total breast cancer related charges for BRCAm and BRCAwt groups respectively (Table 2).
Table 2
Breast Cancer Related Cumulative Charges by BRCA Status and Charge Type
Health care charges ($US) | Overall n = 816 | BRCAm n = 134 | BRCAwt n = 682 | BRCAm vs. BRCAwt |
Mean (SD) | Median (IQR) | Mean (SD) | Median (IQR) | Mean (SD) | Median (IQR) | p-value |
Facilities/ Technical | 29,090 (26,802)33.8%* | 24,027 (34043) | 35,130 (28,878) 40.5% | 33,037 (42,145) | 27,903 (26,234) 32.5% | 22,458 (32,529) | 0.01 |
Physician/ Professional | 15,615 (13,126), 18.2% | 12,441 (17669) | 16,207 (12,198), 18.7% | 15,624 (18,967) | 15,498 (13,306) 18.1% | 11,908 (16,906) | 0.25 |
Pharmacy | 41,277 (69,308) 48.0% | 9,313 (58,716) | 35,352 (51,919) 40.8% | 11,379 (54,399) | 42,442 (72,209) 49.4% | 8,930 (59,659) | 0.65 |
Total Anticancer Treatment | 24,616 (56,779) | 2,018 (15,804) | 16,821 (38,088) | 2,756 (14,673) | 26,148 (59,671) | 1,824 (15,995) | 0.72 |
Other Medication(s) | 16,661 (24,471) | 2,911 (27,834) | 18,531 (24,484) | 6,035 (30,729) | 16,294 (24,470) | 2,609 (26,434) | 0.19 |
Clinical Trial | 56 (347) | 0 (0) | 89 (621) | 0 (0) | 49 (262) | 0 (0) | 0.93 |
Chemotherapy | 7,171 (14,088) | 1,372 (6,575) | 8,439 (14,791) | 2,344 (9,463) | 6,922 (13,944) | 1,180 (6,124) | 0.13 |
Hormonal Therapy | 890 (5,521) | 0 (0) | 769 (4,334) | 0 (0) | 914 (5,728) | 0 (0) | 0.53 |
Biologic Medicine | 16,499 (50,091) | 0 (0) | 7,524 (30,898) | 0 (0) | 18,262 (52,891) | 0 (0) | 0.02 |
Chemotherapy Administration | 0 (5) | 0 (0) | 1 (7) | 0 (0) | 0 (5) | 0 (0) | NA |
Total Charges | 85,982 (94,087) | 55,230 (94,787) | 86,689 (75,937) | 65414 (95894) | 85,843 (97,304) | 54,635 (94,085) | 0.19 |
*Percent contribution of the charge type to total charges; SD – Standard deviation; IQR – Interquartile range |
Comparison of health care cumulative charges between HER2 + and HER2- patients
Breast cancer related charges were significantly higher for HER2 + patients vs. HER2- ($155,858 vs. $69,883; p < 0.001, Fig. 3) which was primarily driven by outpatient charges ($139,322 vs. $52,841, p < 0.001, Fig. 3). In addition, HER2 + patients incurred significantly higher charges across nearly all breast cancer related charge categories (Table 3), especially biologic therapy ($71,855 [$72,075] vs. $732 [$12,692], p < 0.0001; Table 3).
Table 3
Breast Cancer Related Cumulative Charges by Receptor Status and Charge Type
Health care charges ($US) | HER2 + ER+/PR+/HER2 + or ER-/PR-/HER2 + n = 142 | HER2- TNBC or ER+/PR+/HER2- n = 521 | HER2 + vs HER2- |
Mean (SD) | Median (IQR) | Mean (SD) | Median (IQR) | p-value |
Facilities/ Technical | 36,523 (28082) | 34,647 (39,683) | 28,707 (26,418) | 24,207 (32,460) | 0.00 |
Physician/ Professional | 18191 (14195) | 16,138 (17,411) | 15,648 (12,973) | 12,577 (17,458) | 0.04 |
Pharmacy | 101,145 (94,243) | 10,1374 (147,132) | 25,529 (39,646) | 7,303 (42,884) | < 0.0001 |
Total Anticancer Treatment | 82,890 (81,269) | 81,783 (127,300) | 7,929 (21,782) | 1,364 (6,006) | < 0.0001 |
Clinical Trial | 96 (430) | 0 (0) | 39 (199) | 0 (0) | 0.26 |
Chemotherapy | 10,443 (15,582) | 4,417 (14,415) | 6,222 (13,642) | 1,074 (5,461) | < 0.0001 |
Hormonal Therapy | 496 (3,889) | 0 (0) | 935 (5,660) | 0 (0) | 0.46 |
Biologic Therapy | 71,855 (72,075) | 6,5471 (117,006) | 732 (12,692) | 0 (0) | < 0.0001 |
Other Medication(s) | 18,255 (21,988) | 6,517 (29,473) | 17,600 (25,321) | 2,953 (29,228) | 0.02 |
SD – Standard deviation; IQR – Interquartile range |
Comparison of health care cumulative charges by initial treatment setting
Patients seen initially in the neoadjuvant setting had higher mean breast cancer related charges vs. those seen in the adjuvant treatment setting ($117,922 vs. $80,061, p < 0.0001; Fig. 4). Patients receiving neoadjuvant treatment had significantly higher charges across most of the charge categories vs. patients receiving adjuvant treatment (Table 4). Patients with metastatic disease had a mean breast cancer related total charge of $101,969 (Fig. 4).
Table 4
Breast Cancer Total Cumulative Charges by Initial Treatment at Diagnosis and Charge Type
Health care charges ($US) | Surgical Resection n = 73 | Adjuvant n = 553 | Neoadjuvant n = 148 | Adjuvant vs. Neoadjuvant |
Mean (SD) | Median (IQR) | Mean (SD) | Median (IQR) | Mean (SD) | Median (IQR) | p-value |
Breast Cancer related | | | | | | | |
Facilities/ Technical | 23,472 (21,512) | 19,840 (28,345) | 27,486 (24,400) | 22,456 (32,113) | 35,877 (27,496) | 33,984 (38,937) | 0.00 |
Physician/ Professional | 12,942 (10,770) | 10,840 (12,678) | 15,575 (13,091) | 12,449 (17,812) | 17,340 (12,663) | 15,536 (16,820) | 0.04 |
Pharmacy | 19,702 (57,840) | 993 (2,650) | 37,000 (66,360) | 8,531 (51,815) | 64,705 (79,214) | 43,009 (83,327) | < 0.0001 |
Total Anticancer Treatment | 11,491 (43,165) | 0 (0) | 21,564 (53,960) | 2,241 (13,526) | 40,941 (71,342) | 4,556 (57,935) | 0.00 |
Clinical Trial | 47 (196) | 0 (0) | 31 (215) | 0 (0) | 78 (297) | 0 (0) | 0.01 |
Chemotherapy | 3,604 (12,107) | 0 (0) | 7,204 (14,053) | 1,759 (6,352) | 7,376 (10,451) | 3,905 (9,278) | 0.01 |
Hormonal Therapy | 1,022 (5,843) | 0 (0) | 836 (5,814) | 0 (0) | 399 (2,711) | 0 (0) | 0.95 |
Biologic Medicine | 6,818 (36,636) | 0 (0) | 13,492 (46,279) | 0 (0) | 33,088 (66,386) | 0 (40,885) | < 0.0001 |
Chemotherapy Administration | 2 (15) | 0 (0) | 0 (4) | 0 (0) | 0 (0) | 0 (0) | . |
Other Medication(s) | 8,210 (21,536) | 993 (2,559) | 15,436 (23,472) | 2,530 (24,473) | 23,764 (24,934) | 12,018 (42,041) | < 0.0001 |
SD – Standard deviation; IQR – Interquartile range |