Preexisting comorbidity adversely impacts breast cancer treatment and outcomes. We examined the incremental impact of comorbidity undetected until cancer. We followed breast cancer patients in SEER-Medicare from 12 months before to 84 months after diagnosis. Two comorbidity indices were constructed: the National Cancer Institute index, using 12 months of claims before cancer, and a second index for previously undetected conditions, using three months after cancer. Conditions present in the first were excluded from the second. Overall, 6,184 (10.1%) had
Comorbidity adversely impacts the treatment [
Most studies based on SEER-Medicare include some measures of comorbidity, and in a random sample of all SEER-Medicare studies published between 2006 and 2011, 23/30 (77%) included the NCI Comorbidity Index. One important limitation of this index, however, is that it ignores conditions that are undetected in claims until after cancer is diagnosed. Recently, we examined the incidence of undetected comorbidity in breast cancer [
Undetected comorbidity could have additional implications for breast cancer treatment and outcomes. Therefore, in this study we sought to describe risk factors for comorbidity that remained undetected until breast cancer, and to assess the added impact of undetected comorbidity on breast cancer treatment and outcomes.
Presently SEER-Medicare [
Patients were included if they were diagnosed with breast cancer between 2001-01-01 and 2005-12-31, had only one primary cancer diagnosed, and had at least 12 months of Medicare Part A and Part B coverage prior to cancer. They were excluded for the following reasons: male breast cancer, cancer diagnosed before age 65, diagnosis made by death certificate or autopsy, death within the first month following diagnosis, or Medicare enrollment less than 12 months before diagnosis. Patients were followed up from 12 months before cancer until the end of the claims period (2007-12-31) or death, whichever came first. Since SEER reports only the month of cancer diagnosis, the first day of that month was assigned as the date of diagnosis.
Patients were described according to their demographic, clinical, and socioeconomic characteristics [
The SEER-Medicare dataset contains information from the 2000 US Census, reported at the tract level in which the patient lives, for the percent of the population living in poverty and the percent of those aged ≥25 years with some college. We used these as indicators of the socioeconomic status of individual patients in the cohort.
We constructed two indices of comorbidity. In SEER-Medicare, the gold standard for documenting the presence of comorbidity prior to cancer is the NCI Comorbidity Index [
We applied the same algorithms used in the NCI Comorbidity Index to construct an index of undetected comorbidity, which was based on claims from the month of cancer diagnosis up to two months after. For each patient, conditions identified prior to cancer were excluded from the undetected comorbidity index. If chemotherapy or radiation began within three months following cancer diagnosis, the observation period for the undetected comorbidity index was truncated at that time to minimize the risk of misclassifying treatment-related adverse events as undetected conditions. As above, patients were classified as having a score = 0, 1, or ≥2. Since the minimum weight assigned to any condition in either index is one (1), for clarity the term “≥ 1 condition/comorbidity” is used in the Results to describe patients with a score on either the previously detected or undetected comorbidity index of ≥1.
Adjuvant chemotherapy was identified based on Healthcare Common Procedure Coding (HCPCS) “J” codes as recommended by the NCI [
The date of death was assigned by using the Medicare date if available. When the Medicare date was missing but the SEER date was available, the SEER date was used. All other patients were assumed to be alive at the end of the observation period. The cause of death was classified as cancer or other cause.
Multivariable analyses were performed to examine risk factors for undetected comorbidity, as well as associations between undetected comorbidity, adjuvant chemotherapy, and mortality. Both indices of comorbidity were included in analyses of treatment and mortality to assess the incremental impact of undetected comorbidity. The multivariable analysis of adjuvant chemotherapy was limited to those with stage I–III disease [
There were 61,002 patients in the final cohort, of whom 6,184 (10%) had ≥1 undetected comorbidity. The mean (standard deviation) age was 76.0 (6.8), 54.6% were aged >75 years, 61% were diagnosed with
Patient characteristics.
Index of undetected comorbidity | |||||||
---|---|---|---|---|---|---|---|
Overall | Score | ||||||
( |
0 | ≥1 |
|
||||
|
% | ( |
( |
||||
|
% |
|
% | ||||
Age at cancer diagnosis (years) | |||||||
66–70 | 12,361 | 20.3 | 11,412 | 20.8 | 949 | 15.4 | <0.0001 |
71–75 | 15,368 | 25.2 | 14,036 | 25.6 | 1,332 | 21.5 | |
76–80 | 15,108 | 24.8 | 13,576 | 24.8 | 1,532 | 24.8 | |
>80 | 18,165 | 29.8 | 15,794 | 28.8 | 2,371 | 38.3 | |
Race/ethnicity | |||||||
White | 52,270 | 85.7 | 47,048 | 85.8 | 5,222 | 84.4 | <0.0001 |
Black | 4,188 | 6.9 | 3,639 | 6.6 | 549 | 8.9 | |
Hispanic | 2,249 | 3.7 | 2,016 | 3.7 | 233 | 3.8 | |
Other | 2,295 | 3.8 | 2,115 | 3.9 | 180 | 2.9 | |
Year of cancer diagnosis | |||||||
2001 | 12,660 | 20.8 | 11,322 | 20.7 | 1,338 | 21.6 | 0.12 |
2002 | 12,452 | 20.4 | 11,166 | 20.4 | 1,286 | 20.8 | |
2003 | 12,086 | 19.8 | 10,845 | 19.8 | 1,241 | 20.1 | |
2004 | 11,929 | 19.6 | 10,765 | 19.6 | 1164 | 18.8 | |
2005 | 11,875 | 19.5 | 10,720 | 19.6 | 1155 | 18.7 | |
Index of prior comorbidity score |
|||||||
0 | 41,001 | 67.2 | 37,365 | 68.2 | 3,636 | 58.8 | <0.0001 |
1 | 13,480 | 22.1 | 11,952 | 21.8 | 1,528 | 24.7 | |
≥2 | 6,521 | 10.7 | 5,501 | 10.0 | 1020 | 16.5 | |
Stage at diagnosis | |||||||
|
10,167 | 16.7 | 9,618 | 17.6 | 549 | 8.8 | <0.0001 |
I | 26,754 | 43.9 | 24,578 | 44.8 | 2,176 | 35.1 | |
II | 17,165 | 28.1 | 15,080 | 27.5 | 2,085 | 33.7 | |
III | 4,096 | 6.7 | 3,428 | 6.3 | 668 | 10.8 | |
IV | 2,820 | 4.6 | 2,114 | 3.9 | 706 | 11.4 | |
Estrogen (ER) and progesterone (PR) receptor status | |||||||
ER and PR positive | 31,419 | 51.5 | 28,347 | 51.7 | 3,072 | 49.7 | <0.0001 |
ER or PR positive | 8,081 | 13.3 | 7,203 | 13.1 | 878 | 14.2 | |
ER and PR negative | 7,165 | 11.8 | 6,353 | 11.6 | 812 | 13.1 | |
Unknown/missing | 14,337 | 23.5 | 12,915 | 23.6 | 1,422 | 23.0 | |
Histological grade | |||||||
1 | 12,419 | 20.4 | 11,403 | 20.8 | 1,016 | 16.4 | <0.0001 |
2 | 23,407 | 38.4 | 21,090 | 38.5 | 2,317 | 37.5 | |
3 | 15,291 | 25.1 | 13,528 | 24.7 | 1,763 | 28.5 | |
4 | 1,881 | 3.1 | 1,710 | 3.1 | 171 | 2.8 | |
Missing/unknown | 8,004 | 13.1 | 7,087 | 12.9 | 917 | 14.8 | |
Indicators of poor performance | |||||||
0 | 52,460 | 86.0 | 47,599 | 86.8 | 4,861 | 78.6 | <0.0001 |
≥1 | 8,542 | 14.0 | 7,219 | 13.2 | 1,323 | 21.4 | |
Percent in census tract with some college | |||||||
<25% | 21,117 | 34.6 | 18,822 | 34.4 | 2,295 | 37.1 | <0.0001 |
≥25% | 39,885 | 65.4 | 35,996 | 65.7 | 3,889 | 62.9 | |
Percent in census tract living in poverty | |||||||
<5% | 19,951 | 32.7 | 18,276 | 33.3 | 1,675 | 27.1 | <0.0001 |
5–7% | 8,718 | 14.3 | 7,919 | 14.5 | 799 | 12.9 | |
8–12% | 13,566 | 22.2 | 12,177 | 22.2 | 1,389 | 22.5 | |
>12% | 18,767 | 30.8 | 16,446 | 30.0 | 2,321 | 37.5 | |
Type of geographic area | |||||||
Large metropolitan | 34,481 | 56.5 | 31,090 | 56.7 | 3,391 | 54.8 | <0.0001 |
Metropolitan | 17,568 | 28.8 | 15,840 | 28.9 | 1,728 | 27.9 | |
Urban | 3,674 | 6.0 | 3,242 | 5.9 | 432 | 7.0 | |
Less urban/rural | 5,279 | 8.7 | 4,646 | 8.5 | 633 | 10.2 |
Among the 6,184 patients with ≥1 undetected comorbidity, there were a total of 7,593 conditions. The most common were COPD (33% [2,023/6,184] of patients), CHF (18%), diabetes (18% without complications; 4% with complications), myocardial infarction (14%), and CVD (10%). In multivariable logistic regression, factors associated with having ≥1 undetected condition were older age, ≥1 comorbidity detected prior to cancer, ≥1 indicator of poor performance status, advanced stage, histological grade, living in a census tract with more poverty, and living in an urban area. Other race/ethnicity (compared to white) and later year of cancer diagnosis were associated with lower odds of having ≥1 undetected condition (Table
Risk of undetected comorbidity.
OR | 95% CI |
|
||
---|---|---|---|---|
Lower | Upper | |||
Age at cancer diagnosis (years) | ||||
66–70 | Reference category | |||
71–75 | 1.12 | 1.02 | 1.22 | 0.02 |
76–80 | 1.28 | 1.17 | 1.39 | <0.0001 |
>80 | 1.53 | 1.41 | 1.66 | <0.0001 |
Race/ethnicity | ||||
White | Reference category | |||
Black | 1.04 | 0.94 | 1.16 | 0.41 |
Hispanic | 0.94 | 0.81 | 1.08 | 0.39 |
Other | 0.83 | 0.71 | 0.97 | 0.02 |
Year of cancer diagnosis | ||||
2001 | Reference category | |||
2002 | 0.99 | 0.91 | 1.07 | 0.75 |
2003 | 0.98 | 0.90 | 1.07 | 0.68 |
2004 | 0.93 | 0.85 | 1.01 | 0.08 |
2005 | 0.92 | 0.84 | 1.00 | 0.05 |
Index of prior comorbidity score (NCI Comorbidity Index) | ||||
0 | Reference category | |||
1 | 1.20 | 1.13 | 1.28 | <0.0001 |
≥2 | 1.50 | 1.38 | 1.63 | <0.0001 |
Indicators of poor performance | ||||
0 | Reference category | |||
≥1 | 1.30 | 1.21 | 1.40 | <0.0001 |
Stage at diagnosis | ||||
|
Reference category | |||
I | 1.66 | 1.49 | 1.85 | <0.0001 |
II | 2.40 | 2.15 | 2.67 | <0.0001 |
III | 3.26 | 2.87 | 3.71 | <0.0001 |
IV | 5.51 | 4.85 | 6.26 | <0.0001 |
Histological grade | ||||
Well differentiated | Reference category | |||
Moderately differentiated | 1.11 | 1.02 | 1.20 | 0.01 |
Poorly differentiated | 1.15 | 1.05 | 1.26 | <0.01 |
Undifferentiated/anaplastic | 1.25 | 1.05 | 1.50 | 0.01 |
Missing/unknown | 1.14 | 1.03 | 1.27 | 0.01 |
Estrogen (ER) and progesterone (PR) receptor status | ||||
ER and PR negative | Reference category | |||
ER or PR positive | 1.05 | 0.94 | 1.16 | 0.39 |
ER and PR positive | 1.00 | 0.92 | 1.09 | 1.00 |
Unknown/missing | 1.14 | 1.03 | 1.27 | 0.01 |
Percent in census tract with some college | ||||
<25% | Reference category | |||
≥25% | 0.99 | 0.93 | 1.05 | 0.70 |
Percent in census tract living in poverty | ||||
<5% | Reference category | |||
5–7% | 1.07 | 0.98 | 1.17 | 0.12 |
8–12% | 1.17 | 1.08 | 1.27 | <0.0001 |
>12% | 1.34 | 1.25 | 1.45 | <0.0001 |
Type of geographic area | ||||
Large metropolitan | Reference category | |||
Metropolitan | 0.97 | 0.91 | 1.04 | 0.42 |
Urban | 1.14 | 1.02 | 1.28 | 0.02 |
Less urban/rural | 1.09 | 0.99 | 1.20 | 0.08 |
OR: Odds Ratio; CI: Confidence Interval.
In multivariable analysis, undetected comorbidity was associated with lower adjusted odds of receiving adjuvant chemotherapy (Odds Ratio (OR) = 0.81, 95% Confidence Interval (CI) 0.73–0.90,
Adjuvant chemotherapy.
OR | 95% CI |
|
||
---|---|---|---|---|
Lower | Upper | |||
Age at cancer diagnosis (years) | ||||
66–70 | Reference category | |||
71–75 | 0.55 | 0.51 | 0.59 | <0.0001 |
76–80 | 0.25 | 0.23 | 0.27 | <0.0001 |
>80 | 0.05 | 0.04 | 0.05 | <0.0001 |
Race/ethnicity | ||||
White | Reference category | |||
Black | 0.94 | 0.84 | 1.05 | 0.27 |
Hispanic | 1.15 | 0.99 | 1.32 | 0.06 |
Other | 1.13 | 0.98 | 1.31 | 0.10 |
Year of cancer diagnosis | ||||
2001 | Reference category | |||
2002 | 0.95 | 0.87 | 1.04 | 0.26 |
2003 | 0.86 | 0.79 | 0.94 | <0.001 |
2004 | 0.88 | 0.80 | 0.96 | <0.01 |
2005 | 0.79 | 0.72 | 0.86 | <0.0001 |
Index of prior comorbidity score (NCI Comorbidity Index) | ||||
0 | Reference category | |||
1 | 0.96 | 0.90 | 1.03 | 0.28 |
≥2 | 0.74 | 0.66 | 0.82 | <0.0001 |
Index of undetected comorbidity score | ||||
0 | Reference category | |||
1 | 0.81 | 0.73 | 0.90 | <0.0001 |
≥2 | 0.38 | 0.30 | 0.49 | <0.0001 |
Indicators of poor performance | ||||
0 | Reference category | |||
≥1 | 0.56 | 0.51 | 0.62 | <0.0001 |
Stage at diagnosis | ||||
I | Reference category | |||
II | 8.73 | 8.17 | 9.34 | <0.0001 |
III | 21.87 | 19.83 | 24.12 | <0.0001 |
Histological grade | ||||
Well differentiated | Reference category | |||
Moderately differentiated | 1.58 | 1.44 | 1.72 | <0.0001 |
Poorly differentiated | 2.54 | 2.31 | 2.79 | <0.0001 |
Undifferentiated/anaplastic | 2.01 | 1.60 | 2.53 | <0.0001 |
Missing/unknown | 1.51 | 1.33 | 1.71 | <0.0001 |
Estrogen (ER) and progesterone (PR) receptor status | ||||
ER and PR negative | Reference category | |||
Either ER or PR positive | 0.32 | 0.29 | 0.35 | <0.0001 |
Both ER and PR positive | 0.24 | 0.22 | 0.26 | <0.0001 |
Unknown/missing | 0.30 | 0.27 | 0.34 | <0.0001 |
Percent in census tract with some college | ||||
<25% | Reference category | |||
≥25% | 1.02 | 0.95 | 1.08 | 0.65 |
Percent in census tract living in poverty | ||||
<5% | Reference category | |||
5–7% | 0.93 | 0.85 | 1.02 | 0.13 |
8–12% | 0.93 | 0.86 | 1.01 | 0.08 |
>12% | 0.91 | 0.84 | 0.98 | 0.01 |
Type of geographic area | ||||
Large metropolitan | Reference category | |||
Metropolitan | 1.12 | 1.05 | 1.20 | <0.01 |
Urban | 1.14 | 1.01 | 1.29 | 0.03 |
Less urban/rural | 1.06 | 0.95 | 1.18 | 0.32 |
OR: Odds Ratio; CI: Confidence Interval.
Overall, there were 13,208 (22% of cohort) deaths: 5,191 (39% of all deaths) due to cancer; 5,823 (44%) due to other causes; and (17%) unspecified. Among those with ≥1 undetected comorbidity, 42% (2,575) died during the observation period compared to 19% (10,633) of those with no undetected conditions, and the unadjusted mortality rate was significantly higher (
Unadjusted Survival.
In multivariable survival analysis, having undetected comorbidity was associated with increased all-cause mortality (Hazard Ratio (HR) = 1.45, 95% CI 1.38–1.53,
Survival.
All-cause mortality | Cancer mortality | Other-cause mortality | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
HR | 95% CI |
|
HR | 95% CI |
|
HR | 95% CI |
|
||||
Lower | Upper | Lower | Upper | Lower | Upper | |||||||
Age at cancer diagnosis (years) | ||||||||||||
66–70 | Reference category | |||||||||||
71–75 | 1.34 | 1.25 | 1.44 | <0.0001 | 1.27 | 1.15 | 1.40 | <0.0001 | 1.55 | 1.36 | 1.75 | <0.0001 |
76–80 | 1.80 | 1.68 | 1.93 | <0.0001 | 1.47 | 1.34 | 1.62 | <0.0001 | 2.39 | 2.12 | 2.69 | <0.0001 |
>80 | 3.41 | 3.20 | 3.63 | <0.0001 | 2.08 | 1.90 | 2.28 | <0.0001 | 5.74 | 5.15 | 6.41 | <0.0001 |
Race/ethnicity | ||||||||||||
White | Reference category | |||||||||||
Black | 1.04 | 0.97 | 1.11 | 0.26 | 0.91 | 0.81 | 1.02 | 0.09 | 0.89 | 0.79 | 0.99 | 0.03 |
Hispanic | 0.82 | 0.74 | 0.91 | <0.01 | 0.96 | 0.83 | 1.12 | 0.62 | 0.89 | 0.76 | 1.03 | 0.12 |
Other | 0.79 | 0.71 | 0.88 | <0.0001 | 0.94 | 0.79 | 1.11 | 0.45 | 0.74 | 0.63 | 0.89 | <0.01 |
Year of cancer diagnosis | ||||||||||||
2001 | Reference category | |||||||||||
2002 | 0.99 | 0.94 | 1.04 | 0.63 | 0.98 | 0.90 | 1.07 | 0.67 | 0.99 | 0.92 | 1.06 | 0.67 |
2003 | 0.97 | 0.92 | 1.02 | 0.26 | 1.00 | 0.91 | 1.09 | 0.91 | 0.88 | 0.82 | 0.96 | <0.01 |
2004 | 0.91 | 0.86 | 0.97 | <0.01 | 0.90 | 0.82 | 0.99 | 0.03 | 0.87 | 0.79 | 0.95 | <0.01 |
2005 | 0.93 | 0.87 | 1.00 | 0.04 | 0.95 | 0.86 | 1.06 | 0.34 | 0.83 | 0.75 | 0.92 | <0.01 |
Index of prior comorbidity score (NCI Comorbidity Index) | ||||||||||||
0 | Reference category | |||||||||||
1 | 1.45 | 1.39 | 1.52 | <0.0001 | 1.18 | 1.10 | 1.27 | <0.0001 | 1.79 | 1.68 | 1.91 | <0.0001 |
≥2 | 2.05 | 1.95 | 2.16 | <0.0001 | 1.34 | 1.22 | 1.47 | <0.0001 | 2.86 | 2.66 | 3.07 | <0.0001 |
Index of undetected comorbidity score | ||||||||||||
0 | Reference category | |||||||||||
1 | 1.45 | 1.38 | 1.53 | <0.0001 | 1.32 | 1.21 | 1.43 | <0.0001 | 1.58 | 1.46 | 1.71 | <0.0001 |
≥2 | 2.38 | 2.18 | 2.60 | <0.0001 | 1.67 | 1.43 | 1.95 | <0.0001 | 3.31 | 2.94 | 3.73 | <0.0001 |
Indicators of poor performance | ||||||||||||
0 | Reference category | |||||||||||
≥1 | 1.80 | 1.72 | 1.88 | <0.0001 | 1.41 | 1.31 | 1.53 | <0.0001 | 2.15 | 2.02 | 2.29 | <0.0001 |
Stage at diagnosis | ||||||||||||
|
Reference category | |||||||||||
I | 1.79 | 1.66 | 1.94 | <0.0001 | 2.66 | 2.21 | 3.20 | <0.0001 | 1.44 | 1.31 | 1.60 | <0.0001 |
II | 2.95 | 2.73 | 3.19 | <0.0001 | 7.88 | 6.59 | 9.41 | <0.0001 | 1.81 | 1.63 | 2.01 | <0.0001 |
III | 6.03 | 5.52 | 6.58 | <0.0001 | 22.08 | 18.37 | 26.54 | <0.0001 | 2.52 | 2.21 | 2.86 | <0.0001 |
IV | 16.72 | 15.33 | 18.23 | <0.0001 | 85.67 | 71.62 | 102.47 | <0.0001 | 2.62 | 2.21 | 3.10 | <0.0001 |
Histological grade | ||||||||||||
Well differentiated | Reference category | |||||||||||
Moderately differentiated | 1.11 | 1.05 | 1.18 | <0.01 | 1.37 | 1.22 | 1.54 | <0.0001 | 1.06 | 0.98 | 1.14 | 0.13 |
Poorly differentiated | 1.47 | 1.39 | 1.56 | <0.0001 | 2.28 | 2.02 | 2.56 | <0.0001 | 1.14 | 1.05 | 1.24 | <0.01 |
Undifferentiated/anaplastic | 1.38 | 1.23 | 1.56 | <0.0001 | 2.24 | 1.83 | 2.74 | <0.0001 | 0.92 | 0.76 | 1.11 | 0.38 |
Missing/unknown | 1.30 | 1.22 | 1.40 | <0.0001 | 1.82 | 1.60 | 2.07 | <0.0001 | 1.13 | 1.02 | 1.24 | 0.02 |
Estrogen (ER) and progesterone (PR) receptor status | ||||||||||||
ER and PR negative | Reference category | |||||||||||
Either ER or PR positive | 0.69 | 0.65 | 0.74 | <0.0001 | 0.60 | 0.54 | 0.65 | <0.0001 | 0.91 | 0.81 | 1.01 | 0.07 |
Both ER and PR positive | 0.64 | 0.60 | 0.67 | <0.0001 | 0.44 | 0.40 | 0.47 | <0.0001 | 0.96 | 0.87 | 1.05 | 0.36 |
Unknown/missing | 0.87 | 0.82 | 0.93 | <0.0001 | 0.72 | 0.66 | 0.79 | <0.0001 | 1.13 | 1.02 | 1.26 | 0.02 |
Percent in census tract with some college | ||||||||||||
<25% | Reference category | |||||||||||
≥25% | 1.03 | 0.99 | 1.07 | 0.15 | 1.05 | 0.99 | 1.12 | 0.09 | 1.08 | 1.02 | 1.15 | 0.01 |
Percent in census tract living in poverty | ||||||||||||
<5% | Reference category | |||||||||||
5–7% | 1.10 | 1.03 | 1.16 | <0.01 | 1.11 | 1.01 | 1.21 | 0.03 | 1.08 | 0.99 | 1.17 | 0.08 |
8–12% | 1.06 | 1.01 | 1.12 | 0.03 | 0.98 | 0.90 | 1.06 | 0.59 | 1.03 | 0.96 | 1.11 | 0.40 |
>12% | 1.18 | 1.12 | 1.24 | <0.0001 | 1.05 | 0.97 | 1.14 | 0.25 | 1.06 | 0.99 | 1.14 | 0.10 |
Type of geographic area | ||||||||||||
Large metropolitan | Reference category | |||||||||||
Metropolitan | 1.07 | 1.03 | 1.12 | <0.01 | 0.99 | 0.92 | 1.06 | 0.70 | 0.99 | 0.93 | 1.05 | 0.71 |
Urban | 0.97 | 0.89 | 1.05 | 0.38 | 0.81 | 0.70 | 0.93 | <0.01 | 0.76 | 0.67 | 0.86 | <0.0001 |
Less urban/rural | 1.07 | 1.00 | 1.14 | 0.05 | 1.03 | 0.93 | 1.15 | 0.56 | 1.03 | 0.94 | 1.14 | 0.55 |
HR: Hazard Ratio; CI: Confidence Interval.
There was little difference in the magnitude and significance of the coefficients for the previously undetected comorbidity for multivariable models that included versus excluded prior comorbidity as a covariable. For instance, the coefficients for the chemotherapy model were 0.80 and 0.37 for undetected comorbidity scores of 1 and ≥2, respectively, in the model that
We conducted an observational cohort study using SEER-Medicare to describe risk factors for comorbidity that remained undetected until breast cancer and to assess the added impact of undetected comorbidity on breast cancer treatment and outcomes. Advanced age, later stage diagnosis, poor performance status, presence of comorbidity identified prior to cancer, and poverty all were associated with increased risk of undetected comorbidity. The strong monotonic association with cancer stage, as well as the association with poverty, suggests the existence of shared risk factors, such as poor health system contact prior to cancer diagnosis, [
Patients with undetected comorbidity were less likely to receive adjuvant chemotherapy. Furthermore, the effect sizes were larger for undetected comorbidity than for comorbidity detected prior to cancer. For example the Odds Ratio for an undetected comorbidity index score ≥2 was 0.38 compared to 0.74 for a score ≥2 on the index of conditions prior to cancer. Since identification of conditions was based on claims for medical services, one hypothesis is that undetected conditions were more severe because they had not been treated. Others have speculated that one way comorbidity can influence treatment and outcomes in cancer is by distracting the healthcare team from the appropriate management of both [
Undetected comorbidity also was associated with increased overall cancer and other-cause mortality. The impact on other-cause mortality was larger than on cancer mortality. However, all six HRs in the three survival analyses were highly statistically significant, and, in general, HRs for undetected comorbidity were larger than those for comorbidity detected prior to cancer. Again, this supports the hypothesis that undetected comorbidity may be more severe and that it may pose greater challenges to the healthcare team than conditions appearing in claims and, by implication, treated prior to cancer.
It is likely that the impact of undetected comorbidity on cancer mortality is partially explained by its direct impact on the likelihood of receiving adjuvant chemotherapy. The link between adjuvant chemotherapy and survival in breast cancer is well established, and adjuvant chemotherapy was not included in our survival analyses to avoid over adjustment of the models.
Our study has several limitations. First, as discussed above, we cannot rule out the possibility that unobserved factors may have confounded observed associations between the presence of undetected comorbidity and several of the observed risk factors, notably cancer stage at diagnosis. Second, both comorbidity indices in our study are based on claims and consequently have less-than-perfect sensitivity and specificity for the conditions of interest. Therefore, conditions that simply were not found in claims prior to cancer due to limitations of the algorithms in the NCI Comorbidity Index, but which actually had been detected and possibly treated at an earlier date, may have been misclassified as undetected. Third, since SEER includes only the month and not the day of cancer diagnosis, we elected to assign the first day of the month as the date of cancer diagnosis. Had we elected to assign the last day of the month, all conditions classified as previously undetected by virtue of first appearing in the month of cancer diagnosis would have been reclassified as previously detected.
Limitations notwithstanding, our findings indicate that those patients with established risk factors for poor outcomes in breast cancer, including advanced age, later stage, and poor performance status, also are at greatest risk for undetected comorbidity. Furthermore, undetected comorbidity appears to confer greater additional risk of poor outcomes than comorbidity detected prior to cancer, suggesting that it may be more severe and that it may pose additional challenges to the healthcare team. However, these hypotheses would require further investigation.
The authors declare that there is no conflict of interests regarding the publication of this paper.
This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. Editorial assistance in this paper was provided by Kim Merjan and Suzanne Griffiths.