Pregnancy-associated breast cancer: nationwide Dutch study confirms a discriminatory aggressive histopathologic profile

PURPOSE: Breast cancer is the most common type of malignancy in pregnant women, occurring approximately once in every 3000 pregnancies. Pregnancy-associated breast cancer (PABC) is commonly defined as breast cancer diagnosed during or within one year after pregnancy, and it accounts for up to 6.9% of all breast cancers in women younger than 45 years old. Whether these cancers arise before or during pregnancy, and whether they are stimulated by the high hormonal environment of pregnancy, is currently unknown. This study assesses the histopathological profile of PABC in a large Dutch population-based cohort. METHODS: We identified 744 patients with PABC (in this cohort defined as breast cancer diagnosed during or within 6 months after pregnancy) diagnosed between 1988 and 2019, in the nationwide Dutch Pathology Registry (PALGA). An age-matched PALGA cohort of unselected breast cancer patients (≤ 45 years), diagnosed between 2013 and 2016, was used as a control. Histopathologic features of both cohorts were compared. RESULTS: The median age of PABC patients was 34.3 years old (range 19-45 years) and most breast cancers were diagnosed during pregnancy (74.2%). As compared to age-matched controls, PABC patients had tumors of higher Bloom-Richardson grade (grade I: 1.5% vs. 12.4%, grade II: 16.9% vs. 31.3%, grade III: 80.3% vs. 39.5%, p < 0.0001). Furthermore, estrogen (ER)- and progesterone (PR)-receptor expression was less frequently reported positive (ER: 38.9% vs. 68.2% and PR: 33.9% vs. 59.0%, p < 0.0001), while a higher percentage of PABC tumors overexpressed HER2 (20.0% vs. 10.0%, p < 0.0001). The most observed intrinsic subtype in PABC was triple-negative breast cancer (38.3% vs. 22.0%, p < 0.0001), whereas hormone-driven cancers were significantly less diagnosed (37.9% vs. 67.3%, p < 0.0001). CONCLUSION: This study, based on a large population-based cohort of 744 PABC Dutch patients, underlines the more aggressive histopathologic profile compared to age-matched breast cancer patients ≤ 45 years. Further in-depth genetic analysis will be performed to unravel the origin of this discriminating phenotype. It definitely calls for timely detection and optimal treatment of this small but delicate subgroup of breast cancer patients

Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer:study protocol of the INDIBLADE trial

Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).</p

Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial

Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988)

Prognosis of pregnancy-associated breast cancer: inferior outcome in patients diagnosed during second and third gestational trimesters and lactation

Purpose: Pregnancy-associated breast cancer, although most commonly defined as breast cancer diagnosed during pregnancy or ≤1 year following delivery, knows a variety of definitions, likely related to the diversity of reported clinicopathological features and prognosis. More insight into the different breast cancer subgroups during pregnancy, time after delivery and the postpartum period is therefore warranted. Methods: Patients with breast cancer diagnosed during pregnancy or ≤6 months postdelivery were included, and subdivided according to gestational trimester, and postpartum patients according to lactational status. Subgroups were compared to matched non-PABC patients, to investigate the influence of pregnancy and lactation on clinical course and outcome. Results: Overall, 662 PABC patients were included (median age 34 years, median follow-up 6.5 years). PABC patients showed an advanced stage at diagnosis and an inferior 5-years-OS (75.4% vs. 83.2%, p = 0.000) compared to 1392 matched non-PABC patients. In subgroup analysis, first trimester PABC patients showed a significantly lower tumor size and stage as compared to other trimesters. Patients diagnosed during the first trimester and postpartum non-lactating patients had a relatively good OS (81.3% and 77.9%, respectively) versus patients diagnosed during the second and third trimesters and during lactation (OS 60.0%, 64.9% and 65.6%, respectively, p = 0.003). Conclusion: In this large (uniquely specified) PABC cohort, an inferior outcome was found for patients diagnosed within the second and third gestational trimesters and during lactation. These findings indicate that PABC is clinically a heterogeneous group of breast cancer patients that should be redefined based on trimester of diagnosis and lactational status