A prognostic model of early breast cancer relapse after standard adjuvant therapy and comparison with metastatic disease on initial presentation

Abstract

Breast cancer can metastasize at any time during its course, but timing of systemic relapse cannot be predicted by traditional TNM staging. Characteristics of distant recurrence within the first 3 years of diagnosis may identify a group of patients who could benefit from novel strategies to prevent systemic relapse. Of 1,089 patients with breast cancer treated at our institution between January 2007 and May 2011, we identified 76 with de novo metastases (on presentation) and 40 with systemic relapse after a median follow up of 2.2 years. Compared to relapse, de novo metastatic disease was more likely to be grade 1 or 2 (43.1 vs. 18.4 %, p = 0.032), estrogen receptor (ER) positive (69.7 vs. 47.5 %, p = 0.019), progesterone receptor (PgR) positive (56.6 vs. 32.5 %, p = 0.014), and HER2-positive (27.5 vs. 10.3 %, p = 0.035). In the 815 patients with stage I-III disease who were at risk of systemic relapse, univariate analyses were performed for age, tumor size, grade, ER, PgR, HER2, lymph nodes, and TNM stage. A multivariate Cox regression model was built using step-wise model selection and identified 4 covariates that were significantly associated with risk of early relapse: stage-III (p < 0.001), grade-III (p = 0.002), PgR-negative status (p = 0.014), and HER2-negative status (p = 0.033). A risk-score was developed based on the linear combination of these covariates and time-dependent predictive curves were used to evaluate the predictive accuracy of the proposed risk-score. The highest risk-score group had a 1, 2, and 3-year relapse probabilities of 11.5, 41.2, and 52.5 %, respectively. The corresponding 1, 2, and 3-year relapse probabilities for the overall population were 1.2, 4.4, and 6.3 %, respectively. Our proposed model can be used to select patients at high-risk of early relapse who could benefit from enrollment on clinical trials with novel therapies designed for this group.

PAX6 overexpression is associated with the poor prognosis of invasive ductal breast cancer

“…There are few studies reporting PR-negative staining as an independent factor for breast cancer poor prognosis. Only Chen et al (24) suggested that no PR expression was an independent factor for the early recurrence of breast cancer, which is consistent with the present results. However, PR-negative patients include patients with certain triple-negative cancers, which may cause this difference.…”

Twenty-years experience withde novometastatic breast cancer

“…According to previous studies, de novo Stage IV disease seemed to show a favorable biological profile, since they were more likely to be low‐grade tumors with positive hormone receptors when compared with relapsed BC . Conversely, our data suggested that de novo Stage IV disease expresses a more aggressive phenotype compared to earlier stages, characterized by high‐grade tumors, negative hormone receptors, high Ki67 proliferation rate, and positive HER2 status.…”

“…According to previous studies, de novo Stage IV disease seemed to show a favorable biological profile, since they were more likely to be low-grade tumors with positive hormone receptors when compared with relapsed BC. 12,13 Conversely, our data suggested that de novo Stage IV disease expresses a more aggressive phenotype compared to earlier stages, characterized by high-grade tumors, negative hormone receptors, high Ki67 proliferation rate, and positive HER2 status. This could mean that de novo metastatic BC represents a gradual evolution of early BC from good toward poor prognostic factors, whereas relapsed tumors are characterized by a poor prognostic profile since the beginning.…”

Prognostic significance of the progesterone receptor status in Ki67-high and -low Luminal B-like HER2-negative breast cancers

“…Another study that investigated the Ki-67 status during endocrine therapy revealed that Ki-67 was reduced to a greater extent in PgRpositive cancers when compared with PgR-negative cancers [16], suggesting that treating PgR-negative cancers with hormonal therapy could not completely prevent cancer cell activation. Other researchers showed that a PgRnegative status was an important contributor to the relapse risk in early [17] and late periods [18]. The same result was published for metastatic breast cancer.…”