Aims
High‐grade metaplastic breast carcinoma (HG‐MBC) is a rare subtype of invasive breast carcinoma, mostly triple‐negative. Metaplastic carcinomas are less responsive to neoadjuvant chemotherapy ...and are associated with a worse outcome than invasive carcinomas of no special type.
Methods
Clinicopathological characteristics and immunophenotype were retrospectively assessed in a series of 65 patients diagnosed with HG‐MBC between 2005 and 2017 at the Curie Institute (antibody panel: oestrogen receptor ER, progesterone receptor PR, androgen receptor AR, human epidermal growth factor receptor 2 HER2, programmed death ligand‐1 PD‐L1, and trophoblast cell surface antigen 2 TROP2).
Results
The median age at diagnosis was 59.5 years. Six (9%) patients had metastatic disease at diagnosis. Among the nonmetastatic patients receiving neoadjuvant therapy, 26% (5/19) achieved pathological complete response. Most tumours were pT1/pT2 (77%) and 12% were pN+. Histological subtypes (mixed, squamous, mesenchymal, and spindle cell) were 40%, 35.5%, 15.5%, and 9%, respectively. Tumour‐infiltrating lymphocytes were low or moderate except when squamous differentiation was present. Most tumours were triple‐negative (92%). AR and TROP2 were positive in 34% and 85% of the cases, respectively. PD‐L1 was positive in tumour cells in 18% (cutoff: 1% of positive tumour cells) of the cases and in tumour‐infiltrating immune cells in 40% (cutoff: 1% of tumour area) of the cases. Notably, spindle cell and mesenchymal metaplastic breast carcinomas were mostly PDL1‐negative. Lastly, 21 (32.3%) cases were HER2‐low, all being HER2 1+, with no HER2 2+.
Conclusion
Metaplastic breast carcinoma could benefit from tailored therapeutic strategies adapted to the phenotypic specificities of histological subtypes.
Representative immunostaining examples of androgen receptor (A & B), trophoblast cell surface antigen 2 (C & D), and programmed death ligand‐1 (E & F) expression in metaplastic breast carcinoma. Focal nuclear expression of androgen receptor in mesenchymal (A) and squamous (B) component of high‐grade metaplastic breast carcinoma (HG‐MBC). (C) Example of trophoblast cell surface antigen 2 (Trop2) cytoplasmic expression in a squamous component of HG‐MBC. (D) Strong, diffuse, and membranous staining of Trop2, in a squamous component. (E) Example of programmed death ligant‐1 (PD‐L1) expression in tumour cells: cytoplasmic heterogeneous staining of a squamous component. (F) Example of immune cells staining with PD‐L1‐antibody in a squamous component.
Introduction The Residual Cancer Burden (RCB) quantifies residual disease after neoadjuvant chemotherapy (NAC). Its predictive value has not been validated on large cohorts with long-term follow up. ...The objective of this work is to independently evaluate the prognostic value of the RCB index depending on BC subtypes (Luminal, HER2-positive and triple negative (TNBCs)). Methods We retrospectively evaluated the RCB index on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between RCB index and relapse-free survival (RFS), overall survival (OS) among the global population, after stratification by BC subtypes. Results 717 patients were included (luminal BC (n = 222, 31%), TNBC (n = 319, 44.5%), HER2-positive (n = 176, 24.5%)). After a median follow-up of 99.9 months, RCB index was significantly associated with RFS. The RCB-0 patients displayed similar prognosis when compared to the RCB-I group, while patients from the RCB-II and RCB-III classes were at increased risk of relapse (RCB-II versus RCB-0: HR = 3.25 CI 2.1-5.1 p0.001; RCB-III versus RCB-0: HR = 5.6 CI 3.5-8.9 p0.001). The prognostic impact of RCB index was significant for TNBC and HER2-positive cancers; but not for luminal cancers (P.sub.interaction = 0.07). The prognosis of RCB-III patients was poor (8-years RFS: 52.7%, 95% CI 44.8-62.0) particularly in the TNBC subgroup, where the median RFS was 12.7 months. Conclusion RCB index is a reliable prognostic score. RCB accurately identifies patients at a high risk of recurrence (RCB-III) with TNBC or HER2-positive BC who must be offered second-line adjuvant therapies.
To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores.
We analysed 750 female patients with ...invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels.
RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI 0.61-0.71) and fair for Neo-Bioscore (0.70; CI 0.65-0.75). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores.
Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.
Purpose
Few studies evaluated the prognostic value of the presence of lymphovascular invasion (LVI) after neoadjuvant chemotherapy (NAC) for breast cancer (BC).
Methods
The association between LVI ...and survival was evaluated in a cohort of BC patients treated by NAC between 2002 and 2011. Five post-NAC prognostic scores (ypAJCC, RCB, CPS, CPS + EG and Neo-Bioscore) were evaluated and compared with or without the addition of LVI.
Results
Out of 1033 tumors, LVI was present on surgical specimens in 29.2% and absent in 70.8% of the cases. Post-NAC LVI was associated with impaired disease-free survival (DFS) (HR 2.54; 95% CI 1.96–3.31;
P
< 0.001), and the magnitude of this effect depended on BC subtype (
P
interaction
= 0.003), (luminal BC: HR 1.83;
P
= 0.003; triple negative BC: HR 3.73;
P
< 0.001;
HER2
-positive BC: HR 6.21;
P
< 0.001). Post-NAC LVI was an independent predictor of local relapse, distant metastasis, and overall survival; and increased the accuracy of all five post-NAC prognostic scoring systems.
Conclusions
Post-NAC LVI is a strong independent prognostic factor that: (i) should be systematically reported in pathology reports; (ii) should be used as stratification factor after NAC to propose inclusion in second-line trials or adjuvant treatment; (iii) should be included in post-NAC scoring systems.
The role of nipple-sparing mastectomy for breast cancer is controversial, as there is concern regarding its oncologic safety and complication rate. The authors reviewed the literature to quantify the ...incidence of occult nipple malignancy in breast cancer, identify the factors influencing occult nipple malignancy, quantify locoregional recurrence rates, and quantify nipple-sparing mastectomy complication rates.
A search of the literature was performed using PubMed. Key words used were "mastectomy," "nipple involvement," "nipple-sparing mastectomy," "skin-sparing mastectomy," "occult nipple malignancy," "occult nipple disease," and "breast cancer recurrence." Articles were analyzed regarding incidence of occult nipple malignancy, potential factors influencing the incidence of occult malignancy, and recurrence/complications following nipple-sparing mastectomy. The incidence of occult nipple disease was compared between groups using chi-square or Fisher's exact tests for categorical variables and t tests for continuous variables. Values of p < 0.05 were considered significant.
The overall rate of occult nipple malignancy was 11.5 percent. Primary tumor characteristics influencing occult nipple malignancy were tumor-nipple distance less than 2 cm, grade, lymph node metastasis, lymphovascular invasion, human epidermal growth factor receptor-2-positive, estrogen receptor/progesterone receptor-negative, tumor size greater than 5 cm, retroareolar/central location, and multicentric tumors. The overall nipple recurrence rate considered significant was 0.9 percent, and the skin flap recurrence rate was 4.2 percent. Full- and partial-thickness nipple necrosis rates were 2.9 and 6.3 percent, respectively.
Nipple-sparing mastectomy for primary breast cancer is appropriate in carefully selected patients. All patients should have retroareolar sampling. There is strong evidence to suggest that suitable cases are well circumscribed single or multifocal lesions that have a tumor-to-nipple distance greater than 2 cm. Tumors should be grade 1 to 2 and not have lymphovascular invasion, axillary node metastasis, or human epidermal growth factor receptor-2 positivity.
The MonarchE trial explored the use of abemaciclib, a CDK4/6 inhibitor, as an adjuvant treatment in high-risk early-stage luminal-like breast cancer. The study's inclusion criteria, especially the N2 ...status, may require revisiting surgical interventions, including invasive axillary lymph node dissection (ALND)-a procedure that current guidelines generally do not recommend.
We conducted a single-centre, retrospective, observational cohort study on non-metastatic breast cancer patients managed from 2002 to 2011, at the Institut Curie. Data collection involved clinical and histological characteristics plus treatment follow-up.
Out of 8715 treated patients, 721 met the inclusion criteria. Overall, 12% (87) were classified as N2 ( ≥ 4 positive lymph nodes), thus eligible for abemaciclib per "node criterion." Tumour size, positive sentinel lymph nodes, and lobular histology showed a significant correlation with N2 status. Approximately 1000 ALNDs would be required to identify 120 N2 cases and prevent four recurrences.
The MonarchE trial may significantly affect surgical practices due to the need for invasive procedures to identify high-risk patients for adjuvant abemaciclib treatment. The prospect of unnecessary morbidity demands less invasive N2 status determination methods. Surgical decisions must consider patient health and potential treatment benefits.
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