Clarifying Lung Cancer Risk Among Breast Cancer Survivors
Principal Investigator
Name
Keith Sigel
Degrees
M.D., Ph.D.
Institution
The Mount Sinai Hospital
Position Title
Assistant Professor
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-1092
Initial CDAS Request Approval
Nov 9, 2022
Title
Clarifying Lung Cancer Risk Among Breast Cancer Survivors
Summary
Breast cancer (BC) is the second most common cancer among women in the United States, and the second leading cause of death among women after lung cancer. 1 With advances in detection and treatment, there is a rapidly growing population of BC survivors. According to the National Cancer Institute, an estimated 3,771,794 women BC survivors lived in the United States in 2019.2 Second cancers are now a major clinical issue for this growing survivor population; as 1 in 12 patients will develop a second malignancy with lung cancer being the leading cause of death from second cancer among cancer survivors. 3
Surgery followed by adjuvant radiation therapy given to BC patients is associated with reduced risk of local recurrence and survival advantage. 4-7 However, studies have found that radiotherapy (RT) for breast cancer increases the risk of lung cancer in addition to relatively high rates of smoking. 3,8-18 Despite the National Lung Screening Trial (NLST) showing that lung cancer screening with the use of low-dose computed tomography (LDCT) resulted in a 20% reduction in mortality from lung cancer19, the current LC screening guidelines were established for the general population, without consideration of prior cancer survivorship. Participants with cancer diagnosis < 5 years have been excluded from prior randomized trials (RCT). But the effective lung cancer screening eligibility criteria among BC survivors may differ from criteria for the general healthy population. Although most patients with stage I-II BC have a relatively good prognosis and survival, BC survivors’ benefit/risk ratio from LC screening is likely to differ substantially due to a number of factors including competing risks of death (from cancer recurrence or non-breast cancer comorbid conditions). As a result, early harms of LC screening and limited life expectancy due to these competing risks would complicate LC screening regimen selection among BC survivors and result in considerable practice variability. To our knowledge, no randomized data or consistent observational results exist so far to help guide surveillance imagining for LC screening among BC survivors. Therefore, better understanding of lung cancer incidence adjusted for major lung cancer risk factors (including smoking, COPD status, and receipt of chest radiotherapy) is important for quantifying the benefits of lung cancer screening in this population.
The project aims to explore the joint effects of cigarette smoking and radiotherapy (RT) on LC risk by using a multi-racial and ethnic BC survivor population, and further modify PLCOm2012 LC risk model to aid in detecting a second primary lung cancer among BC survivor earlier in the course of the disease. Smoking patterns and smoking cessation, BC history, BC stage and grade, time elapse since BC Diagnosis date till the 2nd primary LC diagnosis and Radiotherapy treatment will be incorporated for secondary lung cancer risk prediction and survival analysis. Additionally, we will estimate non-cancer mortality rates for BC survivors to understand competing risks of death for this group.
Surgery followed by adjuvant radiation therapy given to BC patients is associated with reduced risk of local recurrence and survival advantage. 4-7 However, studies have found that radiotherapy (RT) for breast cancer increases the risk of lung cancer in addition to relatively high rates of smoking. 3,8-18 Despite the National Lung Screening Trial (NLST) showing that lung cancer screening with the use of low-dose computed tomography (LDCT) resulted in a 20% reduction in mortality from lung cancer19, the current LC screening guidelines were established for the general population, without consideration of prior cancer survivorship. Participants with cancer diagnosis < 5 years have been excluded from prior randomized trials (RCT). But the effective lung cancer screening eligibility criteria among BC survivors may differ from criteria for the general healthy population. Although most patients with stage I-II BC have a relatively good prognosis and survival, BC survivors’ benefit/risk ratio from LC screening is likely to differ substantially due to a number of factors including competing risks of death (from cancer recurrence or non-breast cancer comorbid conditions). As a result, early harms of LC screening and limited life expectancy due to these competing risks would complicate LC screening regimen selection among BC survivors and result in considerable practice variability. To our knowledge, no randomized data or consistent observational results exist so far to help guide surveillance imagining for LC screening among BC survivors. Therefore, better understanding of lung cancer incidence adjusted for major lung cancer risk factors (including smoking, COPD status, and receipt of chest radiotherapy) is important for quantifying the benefits of lung cancer screening in this population.
The project aims to explore the joint effects of cigarette smoking and radiotherapy (RT) on LC risk by using a multi-racial and ethnic BC survivor population, and further modify PLCOm2012 LC risk model to aid in detecting a second primary lung cancer among BC survivor earlier in the course of the disease. Smoking patterns and smoking cessation, BC history, BC stage and grade, time elapse since BC Diagnosis date till the 2nd primary LC diagnosis and Radiotherapy treatment will be incorporated for secondary lung cancer risk prediction and survival analysis. Additionally, we will estimate non-cancer mortality rates for BC survivors to understand competing risks of death for this group.
Aims
1. Using PLCO lung cancer screening cohort to quantify the unadjusted and adjusted incidence rate of second primary lung cancer in breast cancer survivors.
2. Recalculate PLCOm2012 risk score accounting for smoking history, BC history, BC stage, receipt of radiotherapy and other previously established PLCOm2012 predictors.
3. Estimate the rate of non-lung cancer and non-breast cancer mortality among breast cancer survivors in PLCO.
Collaborators
Keith Sigel, MD, PhD
Associate Professor. General Internal Medicine.
The Mount Sinai Hospital