Additional Analyses

Additional analyses were undertaken to see if estimates changed after accounting for,

Missing data, competing risks and time-varying diagnostic changes

Hazard ratios and 95% confidence intervals are shown from a proportional hazards survival model of mortality. Data includes all tested patients diagnosed with the specified cancers diagnosed in calendar years 2013-2019. Followup is through 1/1/2022. Followup time (time zero) begins at 6 months after diagnosis. Patients tested after 6 months post-diagnosis are not included in the models. Only treatments occurring before the 6 month post diagnosis date are included in the covariates. Data was missing for stage (4.5%) and grade (5.8%) which was imputed using multiple imputation methods. Five imputed sets were created, and model results were combined using Rubin’s procedures *.

Cancer specific deaths are modeled, and deaths from other causes are treated as competing risks, using a competing risk model as per Fine and Gray **. To reflect potential Covid related underreporting, a time-varying covariate is included in all models, indicating time after 1/1/2020.

Breast, Triple Negative Breast, HER2+ Breast, ER/PR+, HER2- Colorectal Pancreatic
HR Lower Upper HR Lower Upper HR Lower Upper HR Lower Upper HR Lower Upper
Genetic testing result
Negative (ref)
ATM 3.84 1.71 8.62 0.67 0.23 1.96 0.73 0.40 1.33 1.39 0.81 2.40 1.01 0.62 1.66
CHEK2 0.27 0.06 1.22 0.29 0.08 1.07 0.86 0.55 1.34 1.05 0.61 1.80 0.28 0.09 0.88
PALB2 0.74 0.43 1.28 0.95 0.22 4.08 1.26 0.79 1.99 1.41 0.93 2.16 1.56 0.88 2.77
BRCA 1/2 0.66 0.54 0.81 1.18 0.74 1.88 1.23 1.03 1.48 1.60 1.05 2.42 0.70 0.52 0.95
Lynch Syndrome 1.95 0.92 4.14 0.00 0.00 0.00 1.96 1.02 3.77 0.63 0.45 0.88 0.61 0.19 1.97
Other PV 0.96 0.68 1.36 0.74 0.38 1.41 1.09 0.78 1.51 0.86 0.63 1.17 1.14 0.84 1.56
VUS only 1.01 0.86 1.18 0.89 0.69 1.14 0.91 0.79 1.06 0.86 0.72 1.04 1.00 0.81 1.22
Male (vs. Female) 1.10 0.95 1.26 1.02 0.87 1.20
Race and Ethnicity
Non-Hispanic White (ref)
Black 1.11 0.95 1.29 1.43 1.10 1.87 1.27 1.09 1.49 1.03 0.81 1.29 1.12 0.81 1.55
Asian 0.69 0.54 0.88 1.07 0.78 1.46 0.91 0.76 1.09 1.07 0.84 1.37 1.02 0.78 1.33
Hispanic 1.05 0.90 1.23 1.27 0.99 1.64 1.08 0.93 1.25 1.16 0.97 1.41 1.10 0.85 1.43
Other 0.39 0.16 0.94 0.68 0.17 2.68 0.83 0.43 1.62 1.15 0.37 3.61 1.06 0.46 2.46
Age at Diagnosis (decades) 0.99 0.94 1.05 1.10 1.01 1.20 1.22 1.17 1.28 1.14 1.07 1.20 1.13 1.05 1.22
Poverty level
Low (poverty <10%) (ref)
Medium (poverty 10%-19%) 0.92 0.78 1.08 1.00 0.77 1.30 1.19 1.03 1.36 0.99 0.81 1.19 1.17 0.92 1.47
High (poverty > 20%) 1.11 0.92 1.35 1.70 1.25 2.32 1.50 1.25 1.79 1.14 0.88 1.48 1.17 0.84 1.65
Rural (vs Urban) 1.11 0.90 1.37 0.89 0.59 1.33 0.98 0.80 1.20 1.09 0.82 1.44 0.97 0.69 1.36
Married (vs Not Married) 0.97 0.87 1.10 0.82 0.68 1.00 0.80 0.72 0.88 0.93 0.81 1.07 0.91 0.76 1.09
Year of Diagnosis
2013 (ref)
2014 1.15 0.94 1.39 0.99 0.74 1.31 0.83 0.71 0.98 0.86 0.65 1.14 0.84 0.57 1.24
2015 1.11 0.92 1.35 0.81 0.60 1.11 0.84 0.72 0.99 0.89 0.68 1.16 0.70 0.48 1.02
2016 0.88 0.71 1.08 0.89 0.64 1.25 0.77 0.64 0.93 0.63 0.48 0.82 0.65 0.45 0.93
2017 0.86 0.69 1.07 0.86 0.58 1.28 0.63 0.51 0.78 0.62 0.47 0.82 0.61 0.43 0.87
2018 0.61 0.47 0.79 0.73 0.42 1.26 0.63 0.49 0.83 0.56 0.41 0.78 0.41 0.27 0.64
2019 0.47 0.34 0.66 0.73 0.38 1.41 0.55 0.40 0.76 0.28 0.19 0.43 0.32 0.19 0.53
Stage
0 0.27 0.16 0.43 0.36 0.11 1.15 0.29 0.20 0.40 1.84 0.78 4.30 0.00 0.00 0.00
1 (ref)
2 2.59 2.10 3.19 2.90 2.01 4.17 1.85 1.58 2.18 2.39 1.50 3.80 1.41 1.02 1.93
3 9.28 7.49 11.49 8.80 6.04 12.80 5.28 4.42 6.31 4.63 2.83 7.56 1.54 1.11 2.15
4 26.45 20.61 33.96 24.45 16.57 36.07 16.20 13.28 19.75 24.18 14.79 39.51 2.08 1.50 2.88
Grade
1 (ref)
2 1.25 0.73 2.11 0.93 0.53 1.64 1.58 1.32 1.90 1.10 0.88 1.39
3 1.18 0.70 1.98 1.30 0.75 2.28 3.34 2.77 4.03 1.89 1.47 2.43
4 1.02 0.38 2.72 0.67 0.07 6.11 1.64 0.48 5.62 1.53 1.01 2.32
Colon (vs. Rectum) 1.13 0.94 1.36
Surgery (Breast)
Lumpectomy
Unilateral mastectomy 1.77 1.47 2.13 0.58 0.42 0.80 1.33 1.13 1.57
Bilateral mastectomy 1.25 1.03 1.53 1.65 1.21 2.25 1.18 0.99 1.41
Other 1.52 1.15 2.01 1.62 1.16 2.25 0.99 0.76 1.28
No surgery 1.69 1.43 2.00 1.37 0.83 2.26 2.18 1.84 2.58
Surgery (vs. None) (Non-Breast) 0.55 0.46 0.66 0.53 0.43 0.65
Chemotherapy (vs None) 0.89 0.73 1.08 1.48 1.11 1.97 1.22 1.07 1.40 1.23 0.93 1.63 2.19 1.57 3.05
Radiation Therapy (vs None) 1.47 1.21 1.79 0.70 0.55 0.88 0.92 0.79 1.07 1.02 0.81 1.30 0.83 0.63 1.10
HER2-Directed Therapy (vs None) 0.96 0.71 1.30 0.63 0.49 0.80 0.98 0.75 1.26
State: CA (vs. GA) 0.78 0.67 0.91 0.78 0.57 1.07 0.62 0.55 0.71 0.70 0.58 0.83 0.67 0.55 0.82

* Rubin, D.B. (1987), Multiple Imputation for Nonresponse in Surveys, New York: John Wiley & Sons, Inc.

** Fine, Jason P., and Robert J. Gray. “A proportional hazards model for the subdistribution of a competing risk.” Journal of the American Statistical Association 94.446 (1999): 496-509.