The Importance of Second Cancers

The importance of “sequence” and documentation of subsequent cancer continues to be an important aspect of cancer registry abstraction. A study from researchers at the University of Cambridge in England highlights this issue and reports that patients with breast cancer are more likely to develop a second cancer in their lifetime.

Previous studies suggested the risk of developing a non-breast second primary cancer was 24% for women and 27% for men. However, the recent study found the risk can be greater depending on the type of cancer. The study, published in April 2024, used the National Cancer Registration Dataset in the United Kingdom to analyze data from more than 580,000 women and more than 3,500 men who survived breast cancer and were diagnosed between 1995 and 2019.

Here are six findings:

1. Women who survived breast cancer had double the risk of contralateral breast cancer as the general population, and they were at 87% greater risk of endometrial cancer, 58% higher risk of myeloid leukemia and 25% greater risk of ovarian cancer.
2. Women diagnosed with breast cancer before age 50 were 86% more likely to develop a second primary cancer, whereas women diagnosed after age 50 had a 17% increased risk.
3. Women from more socioeconomically disadvantaged backgrounds were at a 35% higher risk of second primary cancer compared to those from less deprived backgrounds. The difference was driven by non-breast cancer risks, particularly for lung, kidney, head and neck, bladder, esophageal and stomach cancers.
4. Male breast cancer survivors were 55 times more likely to develop contralateral breast cancer compared to the general male population.
5. Male breast cancer survivors were 58% more likely to develop prostate cancer.
6. About 3 in every 100 men diagnosed with breast cancer at age 50 or older developed contralateral breast cancer during a 25-year period.

The documentation of subsequent cancers will be an even more critical issue in the future as the number of cancer survivors increases. 

Pregnancy After BRCA-Associated Breast Cancer

Among women carrying germline BRCA pathogenic variants, is pregnancy after breast cancer associated with adverse maternal or fetal outcomes? Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers.

An international, multicenter, hospital-based, retrospective cohort study was conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 who had a germline pathogenic variant in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023.

The study, including 4732 BRCA carriers, showed that 1 in 5 patients conceived within 10 years after a breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with adverse maternal prognosis or fetal outcomes. The cumulative incidence of pregnancy after breast cancer and disease-free survival in this large international cohort of young BRCA carriers may inform care for affected patients.

Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer–specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival.

The importance of aggressive follow-up of cancer patients is again highlighted in this study.

Proton Therapy and the Cancer Registry

Soon, we will be opening a Proton Therapy Treatment Center at my cancer institute. Rather than using a conventional photon beam, the proton treatment has gained favor in its ability to be extremely focused on a specific tumor, while protecting surrounding non-cancerous tissue from radiation injury. Since the first operational proton center opened in 1990, this therapy has transformed from a little-known niche technology to become widespread and well-known to both providers and patients.

When considering appropriate indications for proton therapy, the end goal needs to be prespecified, either dose-escalation beyond that which can reasonably be achieved with photons or toxicity minimization. Classic indications include dose escalation for radio-resistant tumors such as chordoma and chondrosarcoma, with improved tumor control or facilitation of a more comprehensive therapy that may otherwise be too toxic, such as craniospinal irradiation (CSI). Alternatively, late toxicity mitigation for pediatric patients may lead to less risk of secondary malignancies, or a reduction in heart dose for patients with breast cancer may reduce the rate of treatment-related cardiac events and subsequent associated costs of care.

Another intriguing value-based consideration is acute toxicity mitigation, which may be particularly relevant for elderly or frail patients who are less able to tolerate definitive combined modality therapy or may not even be offered curative intent therapy at all. Reducing acute toxicity may reduce treatment breaks, hospital admissions, and consequent medical procedures that outweigh the up-front cost of therapy for vulnerable patients. In addition, patient quality of life and treatment preference are major considerations, and patients should be included in the investigatory process to capture what is most important to them as they weigh their treatment decisions.

Awareness of these indications, considerations, and the complete cost of care will ultimately answer the value-based proposition and better define the role of proton therapy in the field of oncology. Finally, just as conventional radiation treatment has been captured in our cancer registries, the specific characteristics of proton therapy must be included in our patient abstracts, thus allowing for adequate evaluation of outcomes using this exciting, new technology.