BACKGROUND:  Breast Cancer has now become the leading cause of cancer-related deaths among women. In a traditional radical mastectomy, there can be complications that may affect the physiological characteristics of the breast and subsequently cause profound psychological stress to the patients. Hence, latissimus dorsi (LD) flap reconstruction provides an aesthetic approach in patients undergoing mastectomy. The goal is to maximize the flap\'s soft tissue coverage while minimizing the magnitude of donor site defect and complication.
METHODS: A prospective observational study was conducted in the Department of General Surgery, Safdarjung Hospital, New Delhi, India, where 30 breast cancer patients were enrolled and had undergone mastectomy with immediate LD flap reconstruction. Cosmetic assessments using BREAST-Q questionnaires were conducted postoperatively at various intervals starting from postoperative day one, week two, and week six. The subjective evaluation was done by the patient, while a blinded nurse and surgeon did the objective assessment.
RESULTS:  The majority (n=23, 76.7%) were aged 31-50 years. Initial postoperative BREAST-Q scores declined but significantly improved by week six, attributed to gradual wound healing over time, resulting in improved breast shape and contour. The objective scoring done by the blinded surgeon and nurse improved at six weeks compared to two weeks postoperatively. Almost similar outcomes were observed between preoperative and six-week postoperative scores with a significant overall p-value of <0.001. No significant statistical differences were noted between blinded surgeons and nurses for objective scoring.
CONCLUSIONS:  The rising trend of breast cancer in younger demographics emphasizes the importance of balancing cosmetic satisfaction with oncological outcomes. Immediate LD flap breast reconstruction provides a reliable means for soft tissue coverage with acceptable perioperative morbidities for patients undergoing mastectomy. Complication rates were acceptable, with donor site seroma, surgical site infection (SSI), and shoulder weakness among them. They could be prevented or treated (prolonged drain in situ, quilting sutures, and seroma aspiration) or resolved with time (SSI and shoulder function).

OBJECTIVE: Systemic therapy plays a major part in the cure of patients with early breast cancer (eBC). However, personalized treatment concepts are required to avoid potentially harmful overtreatment. Biomarkers are pivotal for individualized therapy. The Notch signalling pathway is widely considered as a suitable prognostic or predictive marker in eBC. This study aimed primarily at assessing the relationship between NOTCH1 mRNA expression levels and histopathological features of breast cancer tumors, as well as clinical characteristics of the correspondent eBC patients. As a secondary aim, we investigated the prognostic and predictive value of NOTCH1 by assessing possible associations between NOTCH1 mRNA expression and recurrence-free interval (RFI) and overall survival after five years of observation.
METHODS: The relative NOTCH1 mRNA expression was determined in 414 tumour samples, using quantitative PCR in a prospective, multicenter cohort (Prognostic Assessment in Routine Application (PiA), 2009-2011, NCT01592825) of 1,270 female eBC patients.
RESULTS: High NOTCH1 mRNA expression was detected in one-third of the tumours and was associated with negative hormone receptor status and high uPA/PAI-1 status. In addition, high NOTCH1 mRNA expression was found to be associated with more RFI related events (adjusted hazard ratio 2.1, 95% CI 1.077-4.118). Patients who received adjuvant chemotherapy and had high NOTCH1 mRNA expression in the tumour (n = 86) were three times more likely to have an RFI event (adjusted hazard ratio 3.1, 95% CI 1.321-7.245, p = 0.009).
CONCLUSIONS: In this cohort, NOTCH1 mRNA expression had a prognostic and predictive impact. Tumours with high NOTCH1 mRNA expression may be less sensitive to cytotoxic treatment and downregulation of the Notch signalling pathway (e.g. by γ-secretase inhibitors) may be valuable for eBC therapy as an individualised treatment option.

Omission of completion axillary lymph node dissection (cALND) in patients undergoing mastectomy with sentinel node (SN) isolated tumor cells (ITC) or micrometastases is debated due to potential under-treatment, with non-sentinel node (NSN) involvement detected in 7% to 18% of patients. This study evaluated the survival impact of cALND omission in a cohort of breast cancer (BC) patients treated by mastectomy with SN ITC or micrometastases. Among 554 early BC patients (391 pN1mi, 163 ITC), the NSN involvement rate was 13.2% (49/371). With a median follow-up of 66.46 months, multivariate analysis revealed significant associations between cALND omission and overall survival (OS, HR: 2.583, p = 0.043), disease-free survival (DFS, HR: 2.538, p = 0.008), and metastasis-free survival (MFS, HR: 2.756, p = 0.014). For Her2-positive or triple-negative patients, DFS was significantly affected by cALND omission (HR: 38.451, p = 0.030). In ER-positive Her2-negative BC, DFS, OS, recurrence-free survival (RFS), and MFS were significantly associated with cALND omission (DFS HR: 2.358, p = 0.043; OS HR: 3.317; RFS HR: 2.538; MFS HR: 2.756). For 161 patients aged ≤50 years with ER-positive/Her2-negative cancer, OS and breast cancer-specific survival (BCSS) were notably impacted by cALND omission (OS HR: 103.47, p = 0.004; BCSS HR: 50.874, p = 0.035). These findings suggest a potential negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. Further randomized trials are needed.

BACKGROUND: There have been concerns about the use of tumor necrosis factor inhibitors (TNFi) for autoimmune disease in patients with recently diagnosed cancer. We assessed the survival of patients with rheumatoid arthritis (RA) and newly diagnosed early breast cancer (BC) treated with TNFi in the first two years after BC diagnosis.
METHODS: We identified patients in two datasets: (1) Optum\'s de-identified Clinformatics® Data Mart Database (CDM), (2) Surveillance, Epidemiology, and End Results program (SEER) and Texas Cancer Registry (TCR) Medicare-linked cohort. We grouped patients according to whether they received TNFi, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) only, or no DMARDs within 2 years after BC. Outcomes were overall survival (OS) and BC-specific survival (BCSS). We conducted landmark analyses at years 1 and 2, with multivariable Cox regressions using propensity scores for adjustment.
RESULTS: In the first year after BC, 165/970 (17.0%) and 201/1246 (16.1%) patients received TNFi in CDM and SEER/TCR-Medicare respectively. In the 1 year landmark, no significant differences in OS were observed between patients treated with TNFi and patients treated with csDMARDs only in CDM (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.42-1.40) or SEER/TCR-Medicare (HR = 0.84, 95% CI 0.54-1.31). BCSS (SEER/TCR-Medicare) was better in patients receiving TNFi than in those receiving csDMARDs only (HR = 0.28, 95% CI 0.08-0.98). In CDM, glucocorticoid therapy had worse OS than those without glucocorticoids (HR = 2.18, 95% CI 1.13-4.18). This was also observed in SEER/TCR-Medicare (not statistically significant). Similar results were observed for the 2 year landmark.
CONCLUSIONS: TNFi treatment during the first two years after early BC was not associated with worse survival.

OBJECTIVE: Adjuvant chemotherapy is often indicated in patients diagnosed with early breast cancer (EBC). Among others, weight gain is one of the observed side effects of both chemotherapy and other cancer treatments; however, the mechanism is not well-described. In this study, we aimed to assess thyroid function before and shortly after the course of chemotherapy for EBC.
METHODS: This is a prospective cohort study of women diagnosed with EBC. The main outcome was the thyroid function and body weight before and after completing chemotherapy. Secondary outcomes were the presence of thyroid autoantibodies and treatment radiation dosage. We included 72 patients treated with adjuvant chemotherapy, whereas 59 patients also received supraclavicular locoregional radiotherapy. Triple-negative breast cancer (BC) patients receiving chemoimmunotherapy were excluded.
RESULTS: After the chemotherapy, we observed an increase in thyroid-stimulating hormone (p = 0.03) and a decrease in free-thyroxine (p = 0.0006), with no significant weight change. The prevalence of autoimmune thyroiditis was low. On average 3 months post-chemo, we found no statistically significant difference in the thyroid function of women treated versus not treated with supraclavicular locoregional radiotherapy.
CONCLUSIONS: Although statistically significant changes in thyroid hormones were observed, this study suggests no obvious clinically significant changes in thyroid function in women with early BC after the course of chemotherapy. The decrease in thyroid function was not related to autoimmunity, non-thyroidal illness, radiotherapy, or high-dose corticosteroids. Further studies with a longer follow-up of thyroid function after adjuvant chemotherapy and supraclavicular locoregional radiotherapy are needed.

The incidence of breast cancer in ≤ 40 yr-old women (YWBC) has been steadily increasing in recent decades. Although this group of patients represents less than 10 % of all newly diagnosed BC cases it encompasses a significant burden of disease. Usually underrepresented in clinical trials, YWBCs are also characterized by late diagnoses and poorly differentiated, aggressive-subtype disease, partly explaining its poor prognosis along with a high recurrence risk, and high mortality rates. On the other hand, YWBC treatment poses unique challenges such as preservation of fertility, and long-term toxicity and adverse events. Herein, we summarize the current evidence in hormone receptor-positive YWBC including specific risk factors, clinicopathologic and genomic features, and available evidence on response to chemotherapy and endocrine therapy. Overall, we advocate for a more comprehensive multidisciplinary healthcare model to improve the outcomes and the quality of life of this subset of younger patients.

Background: We present a detailed description and the preliminary results of our original technique for non-invasive three-dimensional tumor localization in the breast, which was created as an alternative to standard invasive tumor marking before neoadjuvant systemic therapy (NAST), aiming to enable adequate surgery after complete tumor regression. Methods: A detailed description of the technique is provided in the main text. The technique\'s feasibility and precision were assessed in a single-arm, prospective study based on the histological parameters of the adequacy and rationality of the excision of completely regressed tumor beds. Results: Out of 94 recruited patients, 15 (16%) were deemed unsuitable, mainly due to the tumors\' inadequate ultrasound visibility. Among the 79 processed patients, 31 (39%) had complete clinical regression after NAST and were operated on using our technique. The histological parameters of surgical precision (signs of tumor regression: 24/31; microscopic cancer residues: 7/31) were verified in all excised specimens (100% precision). There were no positive margins in seven cases with microscopic residues, indicating our technique\'s capacity to enable oncologically safe post-NAST surgery. Conclusions: The proposed technique is feasible and satisfactorily accurate in determining the location of regressed tumors, thus representing an alternative to invasive tumor marking, especially in surgical centers lacking trained staff and equipment for invasive marking. The technique\'s limitations are mainly related to the inadequate ultrasound visibility of the tumor.

BACKGROUND: The monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials.
METHODS: Between 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed.
RESULTS: Among 2891 HRpos patients, 384 (13.3 %) met the primary monarchE inclusion criteria. The majority (n = 261) qualified due to having ≥ 4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7 %) met the eligibility criteria, with 126 patients (13.7 %) being node-negative. Patients from monarchE with ≥ 4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria.
CONCLUSIONS: Patient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.

BACKGROUND: Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC).
METHODS: We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2-positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta-regression analyses to investigate the effects of multiple covariates.
RESULTS: We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68-2.05). Compared with nonconcurrent or non-anthracycline-containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04-2.12). The linear fixed-effects meta-regression analysis indicated that in trials including more patients with hormone receptor-positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant.
CONCLUSIONS: The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR-negative, HER2-positive tumors to enhance pCR rates, with caution advised for HR-positive tumors due to potential cardiotoxicity.

The availability of radioisotopes for sentinel lymph node biopsy (SLNB) in breast carcinoma is limited in low- and middle-income countries and thus the need for other reliable tracers exists. We aimed to validate the effectiveness of fluorescein sodium (FS) together with methylene blue dye (MBD) for patients with node-negative early breast carcinoma in a prospective cross-sectional study. Patients underwent SLNB using FS and MBD followed by axillary dissection to validate results. Sentinel lymph node (SLN) identification rate and false negative rate were assessed for all three tracers/combinations (MBD, FS, and MBD + FS). We concluded that SLNB using a combination of FS and MBD has an acceptable rate of SLN identification but the addition of FS provided no additional benefit.