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Studying Risk Factors for Second Primary Cancers

Breast cancer is the most common cancer among women in the United States. This year alone, approximately 268,000 women will be newly diagnosed with invasive breast cancer. Breast cancer survivors are at an increased risk of developing a subsequent primary cancer—a new cancer that occurs in a person who has previously had cancer. Although approximately 7% of breast cancer survivors will develop a subsequent cancer in their lifetime, we know very little about the risk factors for new cancers among this population.

To study these risk factors, researchers must first distinguish second primary cancers from two other types of subsequent cancers:

  • Recurrent cancer – the same cancer which is reoccurring in the same area of the body

  • Metastasized cancer – the same cancer that has spread to other areas of the body

This process is difficult in large cancer studies. Just as we can never know for sure why a specific cancer develops in a particular person, we can never know with 100% certainty that a subsequent cancer is a primary subsequent cancer and not a metastasis. However, conducting research on these subsequent primary cancers requires making consistent decisions about whether a specific subsequent cancer was a recurrence, a metastasis, or a new primary cancer.

Dr. Lani Park is an Associate Professor of Research Preventive Medicine at the University of Southern California (USC) who is interested in studying the risk factors for subsequent cancers among California Teachers Study breast cancer survivors. She comes across data that show a de-identified participant had breast cancer twice: once in 2012, and again in 2013. (Remember, this participant is de-identified because whenever CTS data are being analyzed, all the identifying information—such as participants’ names—are hidden from researchers.) Do these two records mean the participant had two cancers? Was the cancer in 2013 a recurrence of the cancer in 2012? Or was it an entirely new cancer?

For her study, Dr. Park has to decide how to classify this participant’s second cancer. She also has to decide whether, among a group of 8,000 CTS breast cancer survivors, 2,000 participants’ additional cancer records are records of recurrence, a metastasis, or a new primary cancer.

As part of her study, Dr. Park is creating a framework to consistently apply rules about whether cancers are metastases, recurrences, or second primary cancers. This framework takes into account SEER guidelines, such as where the second cancer occurred, what it looked like under the microscope, when it was detected, and how those characteristics are different than the first cancer.

Conducting research requires making decisions at scale. By creating this framework, Dr. Park is ensuring that all the cancer cases used in her study are chosen using the same, consistent set of rules. Her work also creates a foundation from which the CTS can approach future research on multiple cancers to better understand their specific risk factors.


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