Study: Age Negatively Associated with Contralateral Breast Cancer Development After Primary Treatment


Further research is necessary to better understand the development and factors that contribute to CBC after PBC treatment.

Although breast cancer (BC) prognosis has improved, primary breast cancer (PBC) is often associated with secondary cancer development. Contralateral breast cancer (CBC) is cancer that develops in the opposite breast in a PBC survivor, and CBC is often considered a new, independent primary cancer rather than metastasis from the initial PBC. A study published in Cancer Reports addresses the risk factors of developing CBC after treating the PBC. In addition, the study assesses the disease-free interval (DFI) and characteristics of PBC as well as the incidence while providing insight into PBC monitoring.

Key Takeaways

1. Contralateral Breast Cancer Risk Factors: To evaluate the development of contralateral breast cancer (CBC) after primary breast cancer, investigators examine the risk factors that may be associated with disease progression. Variables such as age, tumor characteristics, and family history are taken into consideration.

2. Age and CBC Development: The study results indicate that patients older than 60 years of age were negatively associated with CBC development. The research also shows that certain pathological characteristics, such as invasive ductal carcinoma, with a decreased risk of CBC progression.

3. Potential Treatment Plans and Future Research: Understanding CBC risk factors and DFI can assist health care professionals in identifying high-risk individuals while developing personalized treatment plans and monitoring strategies for patients. The authors emphasize that additional research is needed, particularly in larger populations with diverse demographic data to gain further understanding of CBC progression.

This retrospective cohort study focused on metachronous BCs—tumors that manifested at least 6 months after the initial tumor diagnosis. Variables such as patient age, tumor size, estrogen receptor (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, breast histology, chemotherapy, radiotherapy, lymph vascular invasion, family history, lymph node metastasis, hormone therapy, type of surgery, triple negative status, as well as cancer stage and grade were included in the analysis.

A total of 5003 women diagnosed with BC between 2000 and 2020 were enrolled in the study, of which 145 (2.9%) had progressed to CBC within the following years of treatment and the remaining 4858 (93.1%) were considered the PBC group. Patients who had synchronous or metachronous tumors at the time of admission, bilateral synchronous BC, and individuals with a follow-up period of less than 180 days were not included in the study.

Of the patients who developed CBC, 36.92% were younger than 45 years of age—which is younger than the CBC group’s median age (median: 47; range: 17-78)—and had a tumor size of 2 to 4 cm. Further, invasive ductal carcinoma (IDC) was the most common type of BC histology among CBC patients (69.57%). Of the patients with CBC, 72.13% and 66.67% had ER+ and PR+ tumors, respectively, and approximately 70% had negative HER2. Adjuvant chemotherapy was used in 74.63% of patients with PBC, although nearly all patients (83.53%) were treated with external radiotherapy and 61.53% of patients had negative lymph vascular invasion. Further, 45.26% of patients who developed CBC had a mastectomy, but only 10.34% were triple negative.

For patients with PBC, the probability of having a 1-year DFI was 99%, and the probability for 5-year, 10-year, and 20-year DFI was 97%, 96%, and 88%, respectively, and the probability of DFI was higher in patients who were older than 60 years of age compared to patients under 45 years of age and between 45 and 60 years. In addition, the 60 years of age and older group (HR = 0.53; 95% CI: 0.30-0.94) and the IDC type of pathology (HR = 0.61; 95% CI: 0.38-0.97) were negatively associated with CBC progression. Further, a history of BC in the second degree was associated with a 59% increased likelihood of developing CBC; however, BC in the first degree was not associated with CBC.

Patient and physician looking at a mammogram

Image credit: LStockStudio |

Despite the research on BC that has contributed to treatment options and increased survival rates, further research is still needed on the development of CBC after treatment of PBC, according to the study authors. The present study found that the mean age of patients with BC was 49 years, which differs from prior research that indicates the mean age of patients was 61.2 at initial BC diagnosis. Similarly, the median time interval between PBC and CBC was 3.92, but other research reports median time intervals of 6.2 to 6.7 years. The differences in median age and time interval between PBC and CBC may be due to inconsistencies in the populations’ age composition, according to the investigators.

The current study reports a 3% incidence of CBC after 5 years, which is considerable compared to prior research which ranges from 3% to 41.5%. The investigators determined that patients older than 60 years of age had a lower chance of developing CBC; however, other studies show inconclusive reports on the effect of age on the progression of CBC. In addition, was no significant association found between HER2+ status and CBC. Radiotherapy did not show a statistically significant effect of CBC incidence, which is consistent with prior research.

One study limitation is the lack of access to demographic variables (eg, reproductive, lifestyle, and death criteria) to properly adjust for potentially confounding risk factors. Further, the lack of significance in several variables could be a result of the limited population size and the lack of measurement or recognition of potential confounding factors and study conditions.

Although additional research is necessary, the results have to potential to help health care professionals identify patients who are at higher risk of CBC, allowing them to develop proper treatment plans and monitor patients effectively. The identification of CBC and DFI risk factors can improve patients’ outcomes by enabling more personalized plans for patients who may be considered high-risk. The study authors note that future research should enroll a larger participant population and obtain all demographic variables of the patients.


Avatefi, M, HadavandSiri, F, Nazari, SSH, Akbari, ME. Risk factors of developing contralateral breast cancer after first primary breast cancer treatment. Cancer Reports. 2023;e1927. doi:10.1002/cnr2.1927

Recent Videos
1 KOL is featured in this program
1 KOL is featured in this program
1 KOL is featured in this program
Image Credit: © Anastasiia -
1 KOL is featured in this series.
1 KOL is featured in this series.
1 KOL is featured in this program
1 KOL is featured in this program
LGBTQIA+ pride -- Image credit: lazyllama |
Image Credit: © Анастасія Стягайло -