must we always hunt for a sentinel node

The introduction of sentinel lymph node biopsy (SLNB) represented a revolution and one of the latest innovations along the path of minimizing the surgical approach towards breast cancer patients. Some of the advantages of this technique, just to mention two, are firstly that SLNB has the same predictive value and allows one to achieve the same information power as axillary lymph node dissection (ALND). Secondly, it is a functional concept rather than an anatomical entity and therefore it can be applied to special clinical scenarios in which lymphatic drainage might be different than it would be under physiologic conditions. In the paper by Tasevski et al. 1 lymphoscintigraphy (LSG) was applied to 18 patients who previously underwent axillary surgery, which in 15 cases was ALND, allowing at least one sentinel node to be identified in 12 patients. In only 3 of 12 patients LSG demonstrated drainage to the ipsilateral axilla only, while the remainder (9 of 12) had drainage to other sites. The authors point out that ''the argument that prior axillary surgery or breast radiotherapy will have altered the lymphatic drainage of the breast is a stronger argument for reoperative LSG/SLNB than against. If one believes in the concept of lymphatic mapping, then it is in this setting that it is particularly valuable, identifying drainage to unpredictable locations''. And again the authors state that ''preoperative LSG allows the altered lymphatic pathways and sentinel nodes outside the ipsilateral axilla to be identified and biopsied facilitating the surgical staging of the draining regional lymph node''. In my opinion this is really intriguing in the view of a more selective surgery. Nevertheless, only one of the reported 18 patients had a different surgical treatment because of the identification of an axillary contralateral SLN. Actually in this patient 16 positive nodes were found out of 19 removed with a clinically relevant disease which probably might have been diagnosed either clinically or by preoperative imaging. Anyhow, the paper by Tasevsky and coworkers 1 deals with a special clinical scenario and a new field o

Abandoning sentinel lymph node biopsy in early breast cancer? A new trial in progress at the European Institute of Oncology of Milan (SOUND: Sentinel node vs Observation after axillary UltraSouND)

Viewpoints and debates Sentinel lymph node biopsy (SLNB) is the standard approach for axillary staging in patients with early breast cancer. Recent data showed no outcome difference in patients with positive sentinel node between axillary dissection vs no further axillary surgery, raising doubts on the role of SLNB itself. Therefore, a new trial was designed comparing SLNB vs observation when axillary ultra-sound is negative in patients with small breast cancer candidates to breast conserving surgery

overall survival according to type of surgery in young 40 years early breast cancer patients a systematic meta analysis comparing breast conserving surgery versus mastectomy

Abstract Objectives Young age is an independent risk factor for local recurrence after breast conserving surgery (BCS) and whole breast radiotherapy (WBRT) for breast cancer. The aim of this study was to carry out a systematic meta-analysis to address the issue as to whether type of surgery might have an impact on overall survival (OS) of young patients with early breast cancer. Material and Methods We summarized six studies comparing OS between BCS + WBRT vs. mastectomy in young patients (≤40 years) with T1-T2 N0–N + M0 breast cancer. Primary endpoint was OS or distant metastasis free survival (DMFS). Only studies with fully adjusted Hazard Ratios (HR) were analyzed. Summary HRs were calculated through random effects models. We investigated publication bias and heterogeneity by means of sensitivity analyses and meta-regression models. Results Five population-based studies and a pooled study of two clinical trials, for a total of 22598 patients 40 years old or younger, were considered: 10898 patients underwent BCS and 11700 underwent mastectomy. After all the adjustments, including nodal status and tumor size, no difference in risk of death was found between the two groups (10% not sgnificant risk reduction in patients who underwent BCS compared to mastectomy; summary HR = 0·90; 95%CI: 0·81 to 1·00). Between-study heterogeneity was not statistically significant (I 2 = 34% and Chi-square P = 0·15). Heterogeneity investigation did not find any variable influencing results. No indication for publication bias was found (P-value = 0·37). Excluding the only study presenting DMFS the results did not change (HR = 0·88; 95%CI: 0·78 to 1·01). Conclusion Considering all the limitations, from the present meta-analysis carried out on 22598 patients it appears unlikely that mastectomy provides better OS compared to BCS + WBRT in early breast cancer patients aged 40 years or younger

breast conservation and sentinel lymph node biopsy after neoadjuvant systemic therapy

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Real de-escalation or escalation in disguise?

The past two decades have seen an unprecedented trend towards de-escalation of surgical therapy in the setting of early BC, the most prominent examples being the reduction of re-excision rates for close surgical margins after breast-conserving surgery and replacing axillary lymph node dissection by less radical procedures such as sentinel lymph node biopsy (SLNB). Numerous studies confirmed that reducing the extent of surgery in the upfront surgery setting does not impact locoregional recurrences and overall outcome. In the setting of primary systemic treatment, there is an increased use of less invasive staging strategies reaching from SLNB and targeted lymph node biopsy (TLNB) to targeted axillary dissection (TAD). Omission of any axillary surgery in the presence of pathological complete response in the breast is currently being investigated in clinical trials. On the other hand, concerns have been raised that surgical de-escalation might induce an escalation of other treatment modalities such as radiation therapy. Since most trials on surgical de-escalation did not include standardized protocols for adjuvant radiotherapy, it remains unclear, whether the effect of surgical de-escalation was valid in itself or if radiotherapy compensated for the decreased surgical extent. Uncertainties in scientific evidence may therefore lead to escalation of radiotherapy in some settings of surgical de-escalation. Further, the increasing rate of mastectomies including contralateral procedures in patients without genetic risk is alarming. Future studies of locoregional treatment strategies need to include an interdisciplinary approach to integrate de-escalation approaches combining surgery and radiotherapy in a way that promotes optimal quality of life and shared decision-making

Pathological features and survival outcomes of very young patients with early breast cancer: How much is "very young"?

Abstract We collected information on 497 consecutive breast cancer patients aged less than 35 years operated at the European Institute of Oncology. The main aim of the study is to compare biological and clinical features dividing the population by age: Patients aged p = 0.79) and overall survival ( p = 0.99) between the three age groups. This latter findings was confirmed using age as a continuous variable assuming a linear association between age and the outcomes considered, too. In conclusion, our data indicate that the group of patients with breast cancer below 35 years is essentially a homogenous group when classical clinical and immunohistochemical features were considered

breast conserving surgery in 201 very young patients 35 years

Abstract Introduction Surgical treatment of breast cancer in very young patients ( Patients and Methods We retrospectively evaluated outcome and prognostic factors of 201 consecutive patients treated with breast conservation followed by whole breast irradiation between 1997 and 2004 with special attention paid to local control. The average follow up was 72 months (range 13–133 months). Results The mean age was 32 years (Range 20–34). Invasive ductal carcinoma was found in 175 (87.1%) patients. Two (1%) patients had invasive lobular carcinoma. One-hundred and eighteen patients (58.7%) had tumors of 2 cm or smaller. Sentinel lymph node biopsy was performed in 105 (52.2%) patients. One-hundred and ten (54.7%) patients had node-negative disease, 68 (33.8%) patients had 1–3 positive nodes and 23 (11.4%) +4 positive nodes. Eighteen patients (9.0%) developed a local recurrence, 25 (12.5%) developed distant metastases and 23 patients (11.4%) died during follow up. The 5- and 10-year cumulative incidence of local events were 8.2% and 12,3% respectively. The univariate analysis did not identify any variables affecting local disease-free survival. Conclusions Breast conservation in very young patients achieves an acceptable local control rate. No prognostic factors were associated with local events

Ovarian reserve of women with and without BRCA pathogenic variants: A systematic review and meta-analysis.

INTRODUCTION Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type). MATERIAL AND METHODS Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation. RESULTS Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 [95%CI-1.12;-0.35]; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 [95%CI-1.96;-0.05]; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results. CONCLUSION Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve

The generalisability of randomised clinical trials : an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer

Purpose None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1-T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. Trial registration: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015Peer reviewe