Nonsentinel Axillary Lymph Node Status in Clinically Node-Negative Early Breast Cancer After Primary Systemic Therapy and Positive Sentinel Lymph Node: A Predictive Model Proposal.

BACKGROUND: In clinically node-negative (cN0) early stage breast cancer (EBC) undergoing primary systemic treatment (PST), post-treatment positive sentinel lymph node (SLN+) directs axillary lymph node dissection (ALND), with uncertain impacts on outcomes and increased morbidities. PATIENTS AND METHODS: We conducted an observational study on imaging-confirmed cN0 EBC, who underwent PST and breast surgery that resulted in SLN+ and underwent ALND. The association among baseline/postsurgical clinic-pathological factors and positive nonsentinel additional axillary lymph nodes (non-SLN+) was analyzed with logistic regression. LASSO regression (LR) identified variables to include in a predictive score of non-SLN+ (ALND-predict). The accuracy and calibration were assessed, an optimal cut-point was then identified, and in silico validation with bootstrap was undertaken. RESULTS: Non-SLN+ were detected in 22.2% cases after ALND. Only progesterone receptor (PR) levels and macrometastatic SLN+ were independently associated to non-SLN+. LR identified PR, Ki67, and type and number of SLN+ as the most efficient covariates. The ALND-predict score was built based on their LR coefficients, showing an area under the curve (AUC) of 0.83 and an optimal cut-off of 63, with a negative predictive value (NPV) of 0.925. Continuous and dichotomic scores had a good fit (p = 0.876 and p = 1.00, respectively) and were independently associated to non-SLN+ [adjusted odds ratio (aOR): 1.06, p = 0.002 and aOR: 23.77, p < 0.001, respectively]. After 5000 bootstrap-adjusted retesting, the estimated bias-corrected and accelerated 95%CI included the aOR. CONCLUSIONS: In cN0 EBC with post-PST SLN+, non-SLN+ at ALND are infrequent (~22%) and independently associated to PR levels and macrometastatic SLN. ALND-predict multiparametric score accurately predicted absence of non-SLN involvement, identifying most patients who could be safely spared unnecessary ALND. Prospective validation is required.

Evolution of breast conserving surgery-current implementation of oncoplastic techniques in breast conserving surgery: a literature review.

Background and Objective: De-escalation in breast cancer surgery has been a natural evolution since breast conserving surgery (BCS) was introduced in the early 1980s. From Halsted mastectomies to wide local excisions, we are facing nowadays the next trend in form of oncoplastic breast surgery. Oncoplastic breast surgery combines oncological principles with plastic surgery techniques to preserve the breast shape and appearance. The aim of this work is to review recent oncological and quality of live outcomes derived from oncoplastic techniques as well as offer a perspective about its implementation in breast cancer units. Methods: A literature review was conducted to explore the landscape of oncoplastic breast surgery. Key terms related to oncoplastic techniques and breast cancer were used in searches across databases such as PubMed, Embase and Cochrane Library. Inclusion criteria focused on recent articles discussing oncological and quality of life (QoL) outcomes, as well as perspectives on the role of oncoplastic surgery. Key Content and Findings: The research aims to contribute valuable insights into the efficacy and impact of oncoplastic surgery in the context of breast cancer treatment. In this new era of precision medicine, it is more than just healing patients; it is about improving their well-being. We ought to consider specific oncoplasty role in leading this paradigm shift. It is also relevant to define whether these new technical-demanding surgical options can be applied to all patients and if professional training performs adequately to current demands of personalized treatments. Conclusions: The global adoption of oncoplastic BCS is recommended due to its oncological safety and improvement in QoL compared to standard procedures. Emphasizing the need for skilled surgeons in complex cases, collaboration between breast surgeons and scientific societies is urged to certify ongoing educational training in oncoplastic techniques.

Surgical Management and Its Impact on Adjuvant Treatment in Recurrent Ipsilateral Breast Cancer: A Retrospective Cohort Study.

Background: Breast cancer (BC) recurrence, defined as the reappearance of cancer in the ipsilateral breast after primary treatment, poses significant challenges in clinical management. Despite advances in treatment, recurrence rates persist, ranging from 0.6 to 1.5% annually, reaching 10-15% at 20 years. This study aims to analyze the surgical and oncological characteristics of patients with BC recurrence. Methods: This retrospective study includes 56 patients diagnosed with recurrent BC between October 2018 and April 2022. Data were collected from a prospectively maintained surgical database. A descriptive analysis was performed on the initial BC, and the recurrence, including surgical complications, was classified using the Clavien-Dindo system. The success rates of selective sentinel lymph node (SLN) biopsies and aberrant drainages were assessed based on previous surgeries. Results: The cohort included 55 females and 1 male, with a median age of 65.3 years. The mean time to BC recurrence was 11.5 years. Among them, 26.8% underwent breast-conserving surgery, 41.1% had a mastectomy, 21.4% had a mastectomy with reconstruction, and 10.7% had an excision over a previous mastectomy. An SLN biopsy was performed in 78.6% of cases, with higher success rates in those without a previous axillary lymph node dissection (85.7% vs. 63.2%). Aberrant drainage was more frequent in patients with a previous ALND (44.4% vs. 20%). The median follow-up was 41.3 months, with 10.7% experiencing a second recurrence. Conclusions: Repeat breast-conserving surgery with re-irradiation for ipsilateral recurrence is feasible and does not significantly increase complications. SLN biopsy is valuable for restaging and tailoring adjuvant therapies, with ALND not being necessary if re-SLN biopsy shows no drainage. The management of aberrant drainage remains controversial.

Continuous innovation in precision radio-guided surgery.

Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare.

Analysis of Local Recurrence Risk in Ductal Carcinoma In Situ and External Validation of the Memorial Sloan Kettering Cancer Center Nomogram.

BACKGROUND: Adjuvant radiotherapy and hormonotherapy after breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) have been shown to reduce the risk of local recurrence. To predict the risk of ipsilateral breast tumor relapse (IBTR) after BCS, the Memorial Sloan Kettering Cancer Center (MSKCC) developed a nomogram to analyze local recurrence (LR) risk in our cohort and to assess its external validation. METHODS: A historical cohort study using data from 296 patients treated for DCIS at the Hospital Clínic of Barcelona was carried out. Patients who had had a mastectomy were excluded from the analysis. RESULTS: The mean age was 58 years (42-75), and the median follow-up time was 10.64 years. The overall local relapse rate was 13.04% (27 patients) during the study period. Actuarial 5- and 10-year IBTR rates were 5.8 and 12.9%, respectively. The external validation of the MSKCC nomogram was performed using a multivariate logistic regression analysis on a total of 207 patients, which did not reach statistical significance in the studied population for predicting LR (p = 0.10). The expression of estrogen receptors was significantly associated with a decreased risk of LR (OR: 0.25; p = 0.004). CONCLUSIONS: In our series, the LR rate was 13.4%, which was in accordance with the published series. The MSKCC nomogram did not accurately predict the IBTR in this Spanish cohort of patients treated for DCIS (p = 0.10).

Extensive nodal involvement increases the positivity of blue nodes in the axillary reverse mapping procedure in patients with breast cancer.

BACKGROUND: The axillary reverse mapping (ARM) technique has been proposed to prevent arm lymphedema. We conducted this study to assess the feasibility of the technique and the outcomes of patients with neoadjuvant chemotherapy (NAC). METHODS: From July 2009 to May 2010, a prospective study was performed in 36 patients with breast cancer undergoing an ALND. The ARM technique was performed injecting 3 cm(3) of Patent Blue in the ipsilateral arm. Of the 36 patients, 29 patients received NAC previously to the ARM and 7 patients had an ALND and ARM performed as first treatment for positive axillary nodes. RESULTS: The identification rate of blue nodes was 83.3% (30 patients). Sentinel lymph node (SLN) was performed in 15 of 29 (42%) patients in the NAC group. Of these 15, two patients (13%) had a concordance between the blue and the hot node. Blue nodes were positive in 4 (13%) of the 30 patients. CONCLUSIONS: The ARM technique is feasible in patients undergoing NAC. Patients with extensive nodal involvement have increased risk of having positive blue nodes. More studies are needed to assess the subgroup of patients with positive axilla that may have the blue node spared without compromising the oncological treatment.

Intrinsic subtypes and therapeutic decision-making in hormone receptor-positive/HER2-negative metastatic breast cancer with visceral crisis: A case report.

Background: CDK4/6 inhibitors (CDKi), namely, palbociclib, ribociclib, and abemaciclib, combined with either an aromatase inhibitor (AI) or fulvestrant are the standard first/second line for hormone receptor-positive(HR+)/HER2-negative(neg) metastatic breast cancer (MBC). However, the choice of one specific CDKi is arbitrary and based on the physician's experience with the drug, toxicity profile, and patient's preferences, whereas biomarkers for optimal patient selection have not been established so far. Moreover, upfront chemotherapy is still recommended in case of clinical presentation with visceral crisis, despite no evidence of superior benefit for chemotherapy regimens against CDKi-based regimens. Recent correlative biomarker analyses from pivotal trials of palbociclib and ribociclib showed that HR+/HER2-neg MBC might respond differently according to the molecular intrinsic subtype, with Luminal A and B tumors being sensitive to both CDKi, Basal-like being insensitive to endocrine therapy, irrespective of CDKi, and HER2-enriched tumors showing a benefit only with ribociclib-based therapy. Clinical case: We hereby present a paradigmatic clinical case of a woman affected by a relapsed HR+/HER2-neg MBC with bone and nodal lesions, presenting with a visceral crisis in the form of lymphangitis carcinomatosis and diagnosed with a molecularly HER2-enriched tumor, successfully treated with upfront ribociclib + fulvestrant. The patient experienced a complete symptomatic and radiologic remission of the lymphangitis with a partial response as best response, according to RECIST 1.1 criteria. The progression-free survival (PFS) was of 20 months, in line with the median PFS observed in the ribociclib + fulvestrant pivotal trial, where, however, patients with visceral crisis had been excluded. Conclusions: This clinical case confirms in the real-world setting that non-luminal subtypes can be found in HR+/HER2-neg disease and may have potential therapeutic implications in the metastatic setting. It also questions the recommendation of upfront chemotherapy in the case of a visceral crisis in the era of CDKi-based regimens. These issues merit further evaluation in prospective and larger studies.

Aquaporin-4-Positive Triple-Negative Breast Cancer Presenting with Paraneoplastic Neuromyelitis Optica Spectrum Disorder.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory central nervous system disorder that preferentially affects the optic nerve and the spinal cord. Although NMOSD is more commonly an idiopathic autoimmune condition associated with antibodies against aquaporin-4 (AQP4)-IgG, the disease may also occur as a paraneoplastic syndrome in rare instances. In these cases, the expression of AQP4 by the tumor is likely the trigger of the autoimmune response. CASE PRESENTATION: We describe the case of a 32-year-old woman who presented with progressive tetraparesis, cranial involvement, respiratory failure, and spinal cord MRI compatible with longitudinally extensive transverse myelitis, few days after being diagnosed with a T3N1M0 triple-negative right breast cancer. Due to the history of concurrent breast cancer and after ruling out metastatic spinal cord involvement, the possibility of a paraneoplastic origin was raised. AQP4-IgG were found in the serum and CSF by cell-based assay, confirming the diagnosis of NMOSD. The patient was treated with corticosteroids, plasma exchange, and rituximab. Concomitantly, breast cancer therapy was started with an adapted neoadjuvant chemotherapy scheme based on carboplatin and paclitaxel. An initial slight improvement slowed down; so, a right mastectomy with lymphadenectomy was performed. Expression of AQP4 was demonstrated in the tumor. The patient presented a significant neurological improvement after combined treatment regaining muscular balance and strength in upper and lower extremities. CONCLUSION: NMOSD may have a paraneoplastic origin associated with breast cancer and the importance of its early detection since the combination of tumoral and immunosuppressive therapy may improve the patient's prognosis.

Innovación continuada en cirugía radioguiada de precisión / Continuous innovation in precision radio-guided surgery

Desde sus inicios, la medicina nuclear se ha enfrentado a cambios tecnológicos que la han obligado a modificar sus modos operativos y a adecuar sus protocolos. En el campo de la cirugía radioguiada (CRG), la incorporación de la imagen gammagráfica preoperatoria y la detección intraoperatoria con la sonda gamma proporcionó un impulso definitivo a la biopsia del ganglio centinela (GC) para convertirse en el procedimiento estándar de aplicación en el melanoma y el cáncer de mama. Las diversas innovaciones tecnológicas y la adaptación consiguiente de protocolos confluyen en lo disruptivo y lo gradual. Como ejemplos evidentes tenemos la introducción de la tomografía por emisión de fotón único/tomografía computarizada (SPECT/TC) en el campo preoperatorio y las sondas Drop-in (Lightpoint Medical Ltd; Crystal photonics, Eurorad) en el intraoperatorio. Otros aspectos innovadores con posible aplicación en la CRG se basan en la utilización de la inteligencia artificial (IA), navegación y teleasistencia (AU)

Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare (AU)

The prevalence of congenital varicella syndrome after a maternal infection, but before 20 weeks of pregnancy: a prospective cohort study.

OBJECTIVE: To describe the prevalence of congenital varicella syndrome (CVS) within the population of presumably infected pregnant women. METHODS: From 1993 to 2006, all women who presented vesicular rash or a suspicious contact were referred and evaluated in a special unit at our center. Those with residual immunity or were serologically negative were precluded from this study. Positive IgM cases underwent monthly ultrasound scans (US), fetal blood (FB) sampling (including IgM anti VZV and virus culture). Amniotic fluid sample for PCR was added to the diagnosis of positive IgM cases after 1997. RESULTS: A total of 276, of the 566 consulted women, tested positive for IgM anti VZV. Seventeen (6%) were excluded because of an unadvised termination of pregnancy and seven (2.55%) miscarried. Only seven (2.7%) were considered highly likely to have a VZV fetal infection. One case showed positive IgM in FB but developed normally. Another fetus showed positive PCR and infection was confirmed post TOP. Four cases that underwent TOP and histochemistry confirmed no more cases. Complete post-natal follow-up was carried out. The asymptomatic infected child grew healthy until the completion of screening tests when it reached 5 years old. CONCLUSION: The fetal infection rate in this cohort was 0.8%, but the best expected prevalence of CVS, according to our findings, should be 0.39% among infected women. This data should be considered and used during parental counselling.