Clara Morales-Comas

Breast cancer occurring during pregnancy (PrBC) and postpartum (PPBC) is usually diagnosed at more advanced stages compared with other breast cancer, worsening its prognosis. PPBC is particularly aggressive, with increased metastatic risk and mortality. Thus, effective screening methods to detect early PrBC and PPBC are needed. We report for the first time that cell-free tumor DNA (ctDNA) is present in breast milk (BM) collected from patients with breast cancer. Analysis of ctDNA from BM detects tumor variants in 87% of the cases by droplet digital PCR, while variants remain undetected in 92% of matched plasma samples. Retrospective next-generation sequencing analysis in BM ctDNA recapitulates tumor variants, with an overall clinical sensitivity of 71.4% and specificity of 100%. In two cases, ctDNA was detectable in BM collected 18 and 6 months prior to standard diagnosis. Our results open up the potential use of BM as a new source for liquid biopsy for PPBC detection. SIGNIFICANCE: For the first time, we show that BM obtained from patients with breast cancer carries ctDNA, surpassing plasma-based liquid biopsy for detection and molecular profiling of early-stage breast cancer, even prior to diagnosis by image. See related commentary by Cunningham and Turner, p. 2125. This article is featured in Selected Articles from This Issue, p. 2109.

Abstract Background. The standard of care for patients (pts) with an ipsilateral breast tumour recurrence (IBTR) after breast conserving therapy (BCT) is a salvage mastectomy. However there is no solid data providing a clear advantage of radical surgery for IBTR in terms of the outcome for patients with isolated local recurrence after BCT. Nevertheless, there is a growing interest in the feasibility of repeating BCT for these patients (pts). We analyzed the oncological outcomes of repeated breast-conserving therapy (rBCT) related to the immunohistochemical subtype. Materials and methods. Between 2014 and 2020, 35 pts were selected for a 2nd BCT, a new lumpectomy with accelerated partial breast re-irradiation (APBrI), and prospectively followed in three university hospitals in Barcelona. Inclusion criteria were pts older than 50y with a late (> 48m from primary treatment) isolated IBTR less than 2cm, without having primary major radiotherapy toxicity. Oncological outcomes were analyzed. Results. At IBTR, median age was 65y and median time to ITBR was 154m. Patients characteristics are shown in table 1. Tumor’s recurrence was DCIS in 5 pts (14.3%) and invasive carcinoma in 30 pts (85.7%), where Luminal A in 10 pts (33.3%), Luminal B-HER2 negative in 12 pts (40%), Luminal B-HER2 positive in 2 (6.7%), non-Luminal HER2 positive in 3 (10%) and triple negative in 3 (10%). With a median follow-up of 37 months, there were 4 relapses (11.4%), one was a 2nd IBTR (2.85%) after in-situ IBTR, and 3 were metastatic recurrences (8.6%), two after invasive and one after in-situ IBTR. Both metastatic progressions after invasive IBTR, were hormone receptor positive and HER2 negative (Luminal B). There were 2 deaths not related with breast cancer. The 2nd IBTR rate was 2.85%. Five-year regional-free survival, metastasis-free survival, and overall survival was 82.4% (95% IC 52.6 - 94.4 %), %, 84.6% (95% IC 51 - 96 %) and 93.3% (95% IC 61.2 - 99%), respectively. Conclusion. Conservative treatment with breast conserving surgery and APBrI for isolated IBTR after BCT seems like a feasible technique as an alternative to mastectomy in selected patients. Second local recurrences and overall survival are similar to the rates described for salvage mastectomy for isolated ipsilateral breast tumour recurrence. In this cohort of patients, the immunohistochemical subtype tumors with poor prognosis (HER2 positive and triple negative) did not show increase in the local recurrence rate. Table 1.Patients Characteristicsn%Histology TypeIDC2777.1ILC0DCIS514.3Others38.6Differentiation gradeWell differentiated1028.6Moderately differentiated1851.4Poorly differentiated720Estrogen-receptor statusPositive2880Negative720Progesteron-receptor statusPositive1645.7Negative1748.6Unknown25.7HER2 statusOver-expressed617.1Non-over-expressed2674.3Unknown38.6Ki67< 20 %1748.6> 20 %1337.2Unknown514.3IHC subtypeLuminal A1033.3Luminal B1240Luminal B-HER2 positive26.7Non-luminal HER2 positive310Triple negative310IBTR locatedSame quadrant1748.6Different quadrant1645.7Unknwon25.7APBrI3D-CRT927.3IORT26.1IMRT2266.7 Citation Format: Martin Espinosa-Bravo, Victoria Reyes Lopez, Clara Morales Comas, Joaquín Rivero Déniz, Javier de La Torre Fernández de Vega, Irene Vives Roselló, Christian Sisó Raber, Manuel Altabas Gonzalez, Alexandra Giraldo Marin, Inma Alonso, Nuria Argudo, Pau Nicolau, Manel Algara, Xavier Sanz, Xavier Caparrós, Gabriela Oses, Jordi Saez, María Vernet-Tomas, Meritxell Mollà. Safety of conservative surgery with accelerated partial breast re-irradiation for isolated ipsilateral breast cancer recurrence regardless of immunohistochemical subtype. A multicentric prospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-09.

<p>Breast milk charactherization as liquid biopsy specim and comparison to plasma</p>