Clinicopathological features and diagnostic intervals of second primary breast cancer following a prior malignancy: a...

As cancer survival improves, the number of patients at risk of a second primary malignancy (SPM) is increasing. Previous research has focused mainly on SPMs after breast cancer, whereas clinicopathological data on breast cancer arising after another malignancy remain limited, particularly in Chinese populations.

To characterize the demographic, clinicopathological, molecular, and temporal features of second primary breast cancer (SPBC) after a prior malignancy and to conduct an exploratory comparison according to whether the first primary cancer was breast cancer.

A retrospective analysis was performed on 918 patients diagnosed with malignant tumors after prior malignant tumor treatment in Hebei General Hospital from May 2019 to March 2025, among whom 41 patients with SPBC were enrolled. Evaluations were carried out in accordance with the SEER definition of multiple primary tumors, the 8th edition of AJCC TNM staging system and the 2017 St. Gallen consensus on breast cancer molecular typing. Synchronous and metachronous SPBC were defined by intervals of ≤6 months and >6 months, respectively. Statistical analyses were performed using SPSS, and normality was assessed with the Shapiro-Wilk test.

A total of 41 patients were included (40 females and 1 male), with a mean age of 60.3 ± 12.1 years (range, 35-86 years) at SPBC diagnosis. There were 21 cases (51.2%) of left-sided SPBC and 20 cases (48.8%) of right-sided SPBC, and the upper outer quadrant was the most common lesion site accounting for 53.7%. Invasive ductal carcinoma was the predominant pathological type (80.5%). Most cases were in early clinical stages, including stage I (39.0%) and stage II (31.7%). Luminal B was the most prevalent molecular subtype (43.9%), followed by triple-negative breast cancer (22.0%). Breast cancer (namely bilateral breast cancer) was the most common primary tumor (20 cases, 48.8%), followed by gynecological tumors (14.6%, including 5 cases of cervical cancer and 1 case of ovarian cancer), urinary system tumors (12.2%), thoracic tumors (9.8%, all lung cancers) and gastrointestinal tumors (9.8%). The median interval from primary tumor onset to SPBC diagnosis was 60 months (IQR, 46-142 months). Patients with an interval longer than 5 years accounted for 48.8%, those with an interval of 3 to 5 years accounted for 29.3%, and only 2 cases (4.9%) had synchronous tumors with an interval no more than 6 months. The median interval of the prior-breast-cancer subgroup(PBC) was 67 months (IQR, 54.3-153.8 months), and its triple-negative subtype proportion (30.0%) was higher than that of other primary tumor subgroups (14.3%). All patients received surgical treatment for their primary tumors (100%), with chemotherapy exposure rate of 51.2% and radiotherapy exposure rate of 34.1%.

In this selected single-center cohort, 20 of 41 patients had a prior breast cancer, and almost half of SPBC diagnoses occurred more than 5 years after the first malignancy. Luminal B was the most frequent subtype. TNBC was numerically more common in the prior-breast-cancer subgroup, but this difference was not statistically significant. These descriptive findings support risk-adapted long-term surveillance and require validation in larger cohorts with appropriate comparators.