Absolute lymphocyte count as a biomarker for best supportive care transition in metastatic breast cancer.

OBJECTIVES: Time is crucial for patients with metastatic breast cancer (MBC), and clinicians are expected to determine the optimal timing for best supportive care (BSC) transition but no evident marker has been established. We recently revealed that absolute lymphocyte count (ALC) was a prognostic marker for patients with MBC. Thus, we investigated whether ALC could be an indicator of the best timing for the BSC transition. METHODS: 101 patients with MBC were retrospectively investigated, and the relationship between clinicopathological factors, including ALC, and the duration of the last treatment was analysed. RESULTS: Mean ALC significantly gradually decreased during the last three systemic treatments towards BSC transition. Patients of younger age, with special histology type, hormone receptor-positive tumours and low ALC at the start of the last treatment had significantly shorter time-to-treatment-termination (TTT) for the last treatment. When ALC was classified into low and high, the mean TTT of the last treatment in the ALC-low group was significantly shorter (16.4 weeks) compared with that in the ALC-high group (30.2 weeks; p=0.004). CONCLUSIONS: Our data suggest that ALC values, which decrease as MBC progresses, could serve as a potential indicator for determining the optimal timing of BSC transition.

The ratio of intratumoral CD15+ neutrophils to CD8+ lymphocytes predicts recurrence in patients with gastric cancer after curative resection.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) in peripheral blood is an independent prognostic indicator of various cancers. AIMS: In this study, we aimed to investigate the prognostic relevance of the intratumoral immune cell balance in gastric cancer. METHODS AND RESULTS: The study included 82 patients who underwent curative resection for gastric cancer. The intratumoral cluster of differentiation (CD) 15- and CD8-positive cells were evaluated using immunohistochemical staining. Additionally, clinicopathological factors and prognoses were analyzed. Patients with high intratumoral CD15/CD8 ratios had significantly lower overall survival (OS) and relapse-free survival (RFS) compared to those with low CD15/CD8 ratios (p = .0026 and p < .0001, respectively). Additionally, a high CD15/CD8 ratio was associated with lymph node metastasis (p = .019). Patients with high NLR had a significantly lower RFS than those with low NLR (p = .0050). Multivariate analysis revealed that the intratumoral CD15/CD8 ratio, NLR, and venous invasion were independent prognostic indicators of RFS (CD15/CD8 ratio: p < .001, hazard ratio (HR) = 14.7, 95% confidence interval (CI) = 3.8-56.8; NLR: p = .010, HR = 5.4, 95% CI = 1.5-19.6; venous invasion: p = .005, HR = 7.4, 95% CI = 1.8-29.7). CONCLUSION: In summary, we found that the intratumoral CD15/CD8 ratio is an independent prognostic factor following gastric cancer resection and its increase is associated with lymph node metastasis and microscopic lymph vessel invasion. Immunological evaluation with additional aspects of innate immunity may be useful in predicting cancer prognosis.

Efficacy of radiation therapy in Japanese patients with positive margins after breast-conserving surgery.

BACKGROUND: Additional surgical resection is recommended after breast-conserving surgery if the surgical margin is pathologically positive. However, in clinical practice, radiation therapy is sometimes used instead for several reasons. Irradiation may be appropriate for some patients, but real-world data is still insufficient to establish it as standard treatment. We retrospectively investigated the status of local control in patients who received irradiation for positive margins. METHODS: We investigated 85 patients with positive margins after curative partial mastectomy who were treated with irradiation instead of additional excision during the period 2006-2013. The patients received whole-breast irradiation (43.2-50 Gy) using photon beams and additional tumour-bed boost (8.1-16 Gy) using electron beams. Intrabreast tumour recurrence was defined as secondary cancer within the ipsilateral conserved breast. Surgical margin was defined as positive if tumour cell exposure was pathologically confirmed on the margin. RESULTS: Seven patients (8.2%) developed intrabreast tumour recurrence during a mean observation period of 119 months. As to components of positive margin, 76 cases were positive for an intraductal component, of which seven (9.2%) developed intrabreast tumour recurrence. Meanwhile, all nine cases positive for an invasive component were free from intrabreast tumour recurrence. Two of the intrabreast tumour recurrence cases seemed to develop new lesions rather than recurrence, considering tumour location. The cumulative incidence of intrabreast tumour recurrence over 10 years was 6.1%. Limited to true recurrence, intrabreast tumour recurrence incidence was 4.9%. CONCLUSION: Our real-world data supports irradiation as an alternative to additional surgical intervention for positive margins after breast-conserving surgery and offers a basis for further research.

BRCAness of brain lesions reflects a worse outcome for patients with metastatic breast cancer.

PURPOSE: Breast cancer often metastasizes to the central nervous system. Although the prognosis of brain metastases from breast cancer has been considered poor, and systemic therapy has not contributed to an improved prognosis, newer agents are expected to be more effective. BRCAness is defined as the status of homologous recombination deficiency (HRD) in tumor tissue, regardless of the presence of pathogenic germline BRCA1/2 variants. A study employing next-generation sequencing analysis showed that HRD was found relatively frequently in brain metastases of breast cancer patients. However, there have been no studies evaluating BRCAness in brain metastases of breast cancer with more efficient, rapid, and cost-effective methods. METHODS: We retrospectively investigated 17 brain metastases of breast cancer that were surgically resected at our hospital from January 2007 to December 2022. Of these, samples from 15 patients were evaluable for BRCAness by employing multiplex ligation-dependent probe amplification (MLPA) assay. RESULTS: Of the 15 patients, five patients (33%) had tumors with BRCAness. Clinicopathological factors of patients with brain metastases with BRCAness were not statistically different from those of patients who possessed tumors without BRCAness. Patients with brain metastases with BRCAness had shorter overall survival compared to those without BRCAness (BRCAness, median 15 months (95% CI 2-30) vs. non-BRCAness, median 28.5 months (95% CI 10-60); P = 0.013). CONCLUSION: In this study, we evaluated BRCAness in brain metastases of breast cancer with the MLPA method, and found that about one-third of patients had BRCAness-positive tumors. The analysis of BRCAness using MLPA has the potential for practical clinical use.

Relationship Between Daily Dose of Everolimus and Treatment Effect in Patients With Luminal HER2-negative Metastatic Breast Cancer.

BACKGROUND/AIM: Everolimus (EVE)-based treatment is an option for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), but a predictive marker has not yet been established. The recommended dose of EVE in combination with endocrine therapy is 10 mg/day, but due to adverse effects, patients are frequently forced to reduce the dose. However, the correct maintenance dose to achieve a therapeutic effect is still under debate. Employing real-world data, we examined clinicopathological factors to predict the efficacy of EVE-based treatment, particularly focusing on daily dose intensity (DDI). PATIENTS AND METHODS: Ninety-five patients with MBC who received EVE-based treatment in combination with exemestane during the period from 2014 to 2022 were retrospectively investigated. Doses of EVE were reduced as needed and DDI was calculated with total doses of EVE and the duration of the treatment. RESULTS: Mean time-to-treatment-termination (TTT) was 25.4 weeks. Patients with tumors with a high Ki67 labeling index, low absolute lymphocyte count, and small DDI of EVE had significantly shorter TTT (p=0.006, 0.043, and 0.030, respectively). When patients were categorized based on DDI of EVE, patients with DDI ≤5 mg/day had significantly shorter TTT (p=0.002). There were no correlations between RDI and factors such as age, body weight, and numbers of previous treatments for MBC. CONCLUSION: Maintaining a DDI of at least 5 mg/day seems crucial to achieving a therapeutic effect. Our data might be useful for determining the dosage of EVE in clinical practice.

IgG4-related mastitis characterized by skin thickening of the breast: a case report.

BACKGROUND: IgG4-related diseases are characterized by marked infiltration and IgG4-positive plasma cells and fibrosis, and involve multiple organs. However, IgG4-related mastitis is rare. We report a case of mastitis associated with IgG4-related disease. CASE PRESENTATION: A 78-year-old woman visited our hospital with a complaint of multiple subcutaneous nodules. A biopsy of a dorsal subcutaneous mass was performed but did not yield a definitive diagnosis. However, blood tests showed a high level of IgG4, thus she was referred to the department of collagen disease for further examination. Computed tomography (CT) showed a thickening of the skin of the right breast, and the patient was referred to our department. On physical examination, a large area of thickened skin was observed in the right breast without inflammatory breast cancer-like redness, and no mass was palpable. A needle biopsy was performed on an indistinct hypoechoic area in the breast, and she was diagnosed with mastitis associated with IgG4-related disease. Systemic steroid therapy was then administered and the symptoms of multiple skin nodules and mastitis improved. CONCLUSIONS: We reached the diagnosis based on a biopsy of the mammary gland enabling the patient to begin treatment for IgG4-related disease. This case was characterized by breast skin thickening, which is different from inflammatory breast cancer.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

Tissue-Engineered Hepatocyte Sheets Supplemented with Adipose-Derived Stem Cells.

The ability to engineer biologically viable hepatocytes and tissue matrices with long-term functional maintenance has attracted considerable interest in the fields of hepatocyte transplantation and liver tissue engineering. Here, newly developed hepatocyte sheets supplemented with adipose-derived stem cells (ADSCs) were evaluated to assess the effects of ADSCs on hepatocyte function and engraftment into the subcutaneous space. Eight-week-old male C57BL/6J mice were used as donors, and 6-week-old male C.B-17/Icr-scid/scid mice were used as recipients. Hepatocyte-ADSC composite sheets were developed using temperature-responsive culture dishes. Hepatocyte viability in the hepatocyte-ADSC composite sheets was evaluated in an in vitro assay, and the outcome of subcutaneous transplantation of the sheet was evaluated. Hepatocyte viability was sustained in the hepatocyte-ADSC composite sheets in vitro. Albumin secretion was significantly higher (p = 0.015) in the hepatocytes of the hepatocyte-ADSC composite sheets (70.5 µg/mL) than in hepatocyte-only sheets (24.0 µg/mL). Cytokine assays showed that hepatocyte growth factor and interleukin-6 were contributed by ADSCs and not hepatocytes, which were not capable of constitutively secreting them. Immunohistochemically, phosphorylated STAT3 and c-MET expression in hepatocytes in the hepatocyte-ADSC composite sheets was significantly higher than that in the hepatocyte-only sheets. Engraftment of the transplanted hepatocyte-ADSC composite sheets was significantly enhanced without pretreatment of the subcutaneous tissue to induce a vascular network. In the hepatocyte-ADSC composite sheets, the viability of the hepatocytes was significantly maintained as the co-cultured ADSCs provided cytokines, enhancing pivotal cell signaling necessary for hepatocyte activity. Impact statement Hepatocyte transplantation is a safe, less invasive bridge treatment for liver transplantation, but its effectiveness is low and transitory. Herein, we introduce newly developed hepatocyte-adipose-derived stem cell composite sheets with improved strength, easier transplantation, and increased hepatocyte viability in the subcutaneous transplantation compared with hepatocyte-only sheets.

Possible correlation of apical localization of MUC1 glycoprotein with luminal A-like status of breast cancer.

Adjuvant chemotherapy has played a major role in the treatment of hormone receptor-positive breast cancer for many years. To better determine which patient subsets need adjuvant chemotherapy, various gene expression analyses have been developed, but cost-effective tools to identify such patients remain elusive. In the present report, we retrospectively investigated immunohistochemical expression and subcellular localization of MUC1 in primary tumors and examined their relationship to tumor malignancy, chemotherapy effect and patient outcomes. We retrospectively examined three patient cohorts with hormone receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer: 51 patients who underwent 21-gene expression analysis (multi-gene assay-cohort), 96 patients who received neoadjuvant chemotherapy (neoadjuvant chemotherapy-cohort), and 609 patients whose tumor tissue was used in tissue-microarrays (tissue-microarray-cohort). The immunohistochemical staining pattern of the anti-MUC1 monoclonal antibody, Ma695, was examined in cancer tissues, and subcellular localization was determined as apical, cytoplasmic or negative. In the multi-gene assay-cohort, tumors with apical patterns had the lowest recurrence scores, reflecting lower tumor malignancy, and were significantly lower than MUC1-negative tumors (P = 0.038). In the neoadjuvant chemotherapy-cohort, there was no correlation between MUC1 staining patterns and effects of chemotherapy. Finally, in the tissue-microarray-cohort, we found that patients with apical MUC1 staining patterns had significantly longer disease-free-survival and overall survival than other patterns (P = 0.020 and 0.039, respectively). Our data suggest that an apical MUC1 staining pattern indicates luminal A-likeness. Assessment of the subcellular localization of MUC1 glycoprotein may be useful for identifying patients who can avoid adjuvant chemotherapy.

Acute myocarditis during adjuvant therapies for breast cancer: a case report.

BACKGROUND: With the improvement of optimal perioperative drug therapy for breast cancer patients, physicians now have to treat the adverse effects and comorbidities associated with long-term treatments. We report a case who suffered cardiac arrest due to acute myocarditis developed after initiation of adjuvant treatment. CASE PRESENTATION: After completing preoperative chemotherapy and undergoing curative surgery for right breast cancer, a 46-year-old female patient started adjuvant tamoxifen and resumed trastuzumab. Two months later, she complained fever and dyspnea. Blood tests showed a marked increase in hepatic enzymes, and the patient was rushed to our emergency room on suspicion of drug-induced liver injury. In the emergency room, the patient went into cardiac arrest shortly after tachycardia with ST-segment elevation appeared on the monitored electrocardiogram. Resuscitation was started immediately and tracheal intubation, intra-aortic balloon pumping, and extracorporeal membrane oxygenation were started. Coronary angiography results were negative for ischemic heart disease. A diagnosis of fulminant myocarditis was made and steroid pulse therapy and immunoglobulin therapy were started. After the start of treatment, the symptoms of heart failure improved steadily and the patient was discharged on the 28th day. Histological findings of the myocardial biopsy revealed degeneration and necrosis of myocardial cells with marked lymphocytic infiltration, consistent with the histology of lymphocytic myocarditis. Serum cytomegalovirus, coxsackie B virus and adenovirus antibodies were all elevated and these findings were consistent with acute viral myocarditis. CONCLUSIONS: We report a case with strong indications for therapy-induced liver damage, who was ultimately diagnosed with acute viral myocarditis and successfully treated with multidisciplinary therapy. We believe that our findings would be useful for other clinicians in managing similar patients.

Effect of Trastuzumab Deruxtecan on QT/QTc Interval and Pharmacokinetics in HER2-Positive or HER2-Low Metastatic/Unresectable Breast Cancer.

HER2-targeted anticancer therapies may be associated with cardiovascular adverse events. This study evaluated effects of the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd, DS-8201a) on QT/QTc interval and its pharmacokinetics. Patients with heavily pretreated, metastatic HER2-expressing breast cancer were enrolled at seven study sites in Japan. T-DXd was administered intravenously at 6.4 mg/kg on day 1 of each 21-day cycle. Primary end points were baseline-adjusted QTcF interval and pharmacokinetics parameters. Key secondary end points included safety events, serum concentration of T-DXd and DXd at the time of electrocardiographic measurements, and antitumor activity parameters. Among 51 total patients, 47 (92.2%) had HER2-low breast cancer (immunohistochemistry 1+ or 2+ and in situ hybridization-negative/equivocal/missing). Pharmacokinetic parameters after a single dose of T-DXd were consistent with previous studies. After multiple doses, T-DXd showed moderate accumulation (accumulation ratio (cycle 3/cycle 1), 1.35), but DXd showed minimal accumulation (1.09). The upper bound of the 90% confidence interval for mean ΔQTcF interval was < 10 ms at all timepoints, and at mean maximum serum concentration was also < 10 ms. Based on concentration-QT analysis, ΔQTcF increased with increasing concentrations of T-DXd and DXd. No clinically meaningful QTcF prolongation was observed. T-DXd had a manageable safety profile and showed antitumor activity in HER2-low breast cancer. In this study, a T-DXd dose of 6.4 mg/kg, higher than the 5.4-mg/kg dose currently approved for breast cancer, was not associated with clinically relevant QTcF prolongation in heavily pretreated patients with HER2-expressing metastatic breast cancer. This study adds to our understanding of T-DXd for treatment of HER2-low breast cancer.

High platelet-to-lymphocyte ratios in triple-negative breast cancer associates with immunosuppressive status of TILs.

BACKGROUND: Rating lymphocytes (TILs) are a prognostic marker in breast cancer and high TIL infiltration correlates with better patient outcomes. Meanwhile, parameters involving immune cells in peripheral blood have also been established as prognostic markers. High platelet-to-lymphocyte ratios (PLRs) and neutrophil-to-lymphocyte ratios (NLRs) are related to poor outcomes in breast cancer, but their mechanisms remain unknown. To date, TILs and these parameters have been examined separately. METHODS: We investigated the relationship between TILs and the peripheral blood markers, PLR and NLR, in the same patients, using surgical specimens from 502 patients with invasive breast carcinoma without preoperative chemotherapy. For analysis of triple-negative breast cancer (TNBC) patient outcomes, 59 patients who received preoperative chemotherapy were also examined. For immune cell profiling, multiplexed fluorescent immunohistochemistry (mfIHC) of CD3, CD4, CD8, FOXP3 and T-bet, was conducted. RESULTS: A positive correlation between PLR and TIL was observed in TNBC (P = 0.013). On mfIHC, tumors in patients with high PLR and NLR contained more CD3+CD4+FOXP3+ T-cells (P = 0.049 and 0.019, respectively), while no trend was observed in CD8+ T-cells. TNBC patients had different patterns of outcomes according to TIL and PLR, with the TIL-high/PLR-low group having the lowest rate of disease relapse and death, and the longest distant metastasis-free and overall survivals, while the TIL-low/PLR-high group had the shortest survivals. CONCLUSIONS: Our data suggest that the combination of PLR with TIL assessment may enable more accurate prediction of patient outcomes with TNBC.

Multicenter Randomized Open-Label Phase II Clinical Study Comparing Outcomes of NK105 and Paclitaxel in Advanced or Recurrent Breast Cancer.

Background: NK105 is a paclitaxel (PTX)-incorporating "core-shell-type" polymeric micellar nanoparticle formulation composed of block copolymers (polyethylene glycol and a polyamino acid). The efficacy and safety of NK105 and paclitaxel in advanced or recurrent breast cancer have never been compared at equivalent dose levels. Patients and Methods: Patients were randomly assigned to either NK105 or PTX in a 1:1 ratio. The study drug was administered on Day 1, 8, and 15 of a 28-day cycle with 80 mg/m2. The primary endpoint was overall response rate (ORR), secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events. Results: A total of 123 patients (NK105, n=62; PTX, n=61) received one of the two drugs. There was no significant difference in ORR, the median PFS, or OS (NK105 group: 41.9%, 9.1, and 27.5 months, respectively; PTX group: 45.9%, 7.8, and 32.4 months, respectively). Neutropenia occurred more frequently in the NK105 group, but most patients did not require granulocyte-colony stimulating factor or dose-reduction. The median time to onset of peripheral sensory neuropathy (PSN) in the NK105 group was significantly longer than that in the PTX group (p=0.001), and PSN (≥ grade 3) was not observed in the NK105 group. Conclusion: Weekly NK105 administration was well-tolerated. Efficacy was similar in both groups. The PSN profile was better in the NK105 group.

Absolute lymphocyte count decreases with disease progression and is a potential prognostic marker for metastatic breast cancer.

PURPOSE: Peripheral blood parameters such as the neutrophil-to-lymphocyte ratio (NLR) are prognostic markers for breast cancer patients. For instance, patients with a high NLR have a poor prognosis. Meanwhile, high absolute lymphocyte count (ALC) is reportedly a predictive factor for some chemotherapies. However, the underlying mechanisms behind how these markers relate to patient outcomes and how these markers change during the clinical course of patients with metastatic breast cancer (MBC) remains unknown. METHODS: We retrospectively investigated 156 patients who were treated for MBC and eventually transitioned to best supportive care (BSC) at our hospital between January 2017 and December 2021. Changes in peripheral blood parameters during MBC treatments and their association with patient outcomes were examined. RESULTS: From the time of MBC diagnosis (baseline) through to the transition to BSC, ALC became significantly lower, while the NLR and platelet-to-lymphocyte ratio (PLR) became significantly higher (p < 0.001 for all). This association was independent of hormone receptor status. Cox proportional hazard modeling found patients with hormone receptor-negative and a lower baseline ALC had a significantly shorter overall survival (p = 0.030 and p = 0.019, respectively). CONCLUSION: We observed that peripheral blood markers gradually changed with MBC disease progression. Our data suggest that baseline ALC may be a potential prognostic marker after recurrence.

Associations of social capital and health at a city with high aging rate and low population density.

Maintaining physical and mental health of older people is one of the important issues to be addressed in the aging society. Social capital, defined as the resources available to members of social groups, has recently attracted attention as a factor influencing public health. Most of the previous studies targeted various communities having different aging rates or population densities at once to examine the associations of social capital and health outcomes. However, the results of those studies are not always consistent. Moreover, because few studies have targeted a particular advanced aging society, associations of social capital and health at such societies have remained unknown. This study examined how social capital associates with health at a particular city having a very high aging rate and low population density. We targeted Iwamizawa city, Hokkaido, Japan, which is one of the most advanced aging areas, with an aging rate of 36.6% and a population density of 165/km2. We analyzed self-administered questionnaire data obtained from "HELLO (HEalth, Lifestyle, and LOcal community of Iwamizawa citizen) Study" in 2018. The sample comprised 1237 individuals aged 65 and older. Following previous studies, we regarded three items-social cohesion, reciprocity, and civic participation-as social capital indices, and targeted two health outcomes: self-rated health (SRH) and degree of depression. Multilevel Poisson regression analyses were used to calculate prevalence ratios (PRs). We found that at the individual-level, the PR (95% confidence interval) of having poor SRH among those with more civic participation was 0.81 (0.71-0.93), and that of being depressed among those with more social cohesion was 0.32 (0.21-0.51), even after adjusting for compositional factors. We also found that the community-level civic participation significantly correlated with aging rate. Our findings indicate that social capital positively associates with older people's health at the advanced aging city.

Successful treatment with steroid pulse therapy for a COVID-19 case with progressive respiratory failure during treatment for pleural metastasis of breast cancer.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients are at high risk for developing severe conditions if other comorbidities are present, such as advanced cancer. Although the regulation of immune response is thought to play an important role in the treatment of coronavirus disease 2019 (COVID-19), physicians often have difficulties in selecting the most appropriate treatment. Furthermore, the impact that interrupting breast cancer treatment due to a COVID-19 infection has on patient outcomes is still unknown. Herein we report a case of advanced breast cancer in a patient whose COVID-19 acute respiratory failure was successfully treated with minimal interruption to their anticancer therapy for recurrent breast cancer. CASE PRESENTATION: A 48-year-old woman developed carcinomatous pleurisy after curative surgery for breast cancer. One month after the initiation of targeted therapy with palbociclib and fulvestrant, the pleural effusion decreased, but soon after she developed a COVID-19 infection. Dexamethasone (8 mg/day) was administered due to a prolonged fever, but her respiratory symptoms got worse and pneumonia appeared on a computed tomography (CT) scan 7 days after hospitalization. Thus, steroid pulse therapy (methylprednisolone 1000 mg/day) was administered for 3 days. Her respiratory condition rapidly improved. Two weeks after hospital discharge, complete regression of pneumonia was confirmed on CT scan, and her targeted therapy was resumed at the same dose and strength. More than 6 months later, her metastatic disease remains stable while on the same treatment. Retrospective analysis of the patient's neutralizing antibodies found the neutralizing activity was low in the early stages of infection, but became high after recovery. This suggests the patient acquired an immunity to SARS-CoV-2 through the infection, despite having a mild myelosuppression due to treatment for recurrent breast cancer. CONCLUSIONS: Steroid pulse therapy is available worldwide, and may have an important role in cancer patients who develop severe pneumonia from SARS-CoV-2, by enabling them to avoid any long-term disruption to anticancer therapy. Moreover, it might also be useful when antiviral therapies lose their efficacy due to mutations of the virus, such as the Omicron variant. A critical element in cases such as this one is that treatment decisions are made by a team of specialists, including pulmonologists.

Eribulin improved the overall survival from the initiation of first-line chemotherapy for HER2-negative advanced breast cancer: a multicenter retrospective study.

BACKGROUND: Eribulin methylate (eribulin) improved the overall survival (OS) of eribulin-treated patients with HER2-negative advanced breast cancer (ABC) in prospective and retrospective studies. However, the effect of eribulin on OS as first-line chemotherapy and the characteristics of the patients who benefited from eribulin remain unclear. METHODS: Between January 2011 and December 2016, 301 patients with HER2-negative ABC who started first-line chemotherapy at 3 institutions were retrospectively evaluated for OS from the initiation of first-line chemotherapy. RESULTS: We identified 172 patients (119 estrogen receptor-positive [ER+], 47 ER-, 6 unknown) who received eribulin (eribulin group) and 129 patients (92 ER+, 31 ER-, 6 unknown) who did not receive eribulin (non-eribulin group). The median OS from the initiation of first-line chemotherapy in the two groups was not statistically significant (869 vs. 744 days, P = 0.47, log-rank); however, in patients who received eribulin in later lines (≥3rd-line) and who had a history of perioperative chemotherapy with anthracycline- and/or taxane-based regimens, the median OS improved (1001 vs. 744 days, P = 0.037; and 834 vs. 464 days, respectively P = 0.032, respectively; Wilcoxon). Multivariate analyses revealed that a history of perioperative chemotherapy with anthracycline- and/or taxane-based regimens was a predictive factor (hazard ratio, 0.39; 95% confidence interval, 0.21-0.70) for OS. CONCLUSIONS: This study successfully identified subgroups of HER2- ABC patients with improved OS by eribulin therapy. Selecting patients according to their background and line of treatment will maximize the efficacy of eribulin therapy.

Shorter duration of first-line chemotherapy reflects poorer outcomes in patients with HER2-negative advanced breast cancer: a multicenter retrospective study.

Post-progression survival affects overall survival (OS) in patients with HER2-negative advanced breast cancer (HER2-ABC); thus, the optimal choice of first-line chemotherapy (1LCT) remains controversial. We investigated patients with HER2-ABC focusing on their sensitivity to 1LCT. We retrospectively analyzed patients with HER2-ABC who received 1LCT between January 2011 and December 2016 in three participating institutions. We identified 149 patients in the shorter and 152 patients in the longer time to treatment failure (TTF) groups. The median OS was significantly longer in the longer TTF group (hazard ratio [HR] 0.44, P < 0.001, log-rank). In the shorter TTF group, OS of patients who received paclitaxel plus bevacizumab (PB) therapy was significantly inferior to that of those who received chemotherapy other than PB (HR 2.57, P < 0.001, log-rank), and subsequent eribulin therapy significantly improved OS from 1LCT initiation (Wilcoxon P < 0.001); multivariate analyses showed that 1LCT PB therapy was an independent risk factor for poorer OS (HR 2.05, P = 0.003), while subsequent eribulin therapy was an independent prognostic factor for better OS (HR 0.56, P = 0.004). OS was significantly poorer in patients with HER2-ABC with a shorter duration of 1LCT, including PB therapy, while subsequent eribulin therapy improved OS.

The Real-world Outcomes of Patients With Advanced Invasive Lobular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma: A Review at a Single Institution.

BACKGROUND: The real-world outcomes of patients with advanced invasive lobular carcinoma (ILC) of the breast are unclear because of its rarity. PATIENTS AND METHODS: We identified 435 patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer treated at our Institute between 2002 and 2019, and analyzed their outcomes retrospectively. RESULTS: We identified 29 patients with advanced ILC. At presentation, they had a lower rate of lung metastasis (p=0.0053) but a higher rate of stomach metastasis (p=0.0379) compared with other patients with advanced breast cancer. Median overall survival did not differ; however, multivariate analyses showed that ILC histopathology was a risk factor for poorer overall survival (hazard ratio=3.43, p=0.0038) in patients with de novo stage IV ER+ HER2- breast cancer. Patients with ILC showed a markedly different patten of subsequent metastasis, such as less in the lung and more in the stomach, leptomeninges, and bone marrow. CONCLUSION: According to our retrospective study, in patients with de novo stage IV ER+ HER2- breast cancer, ILC histopathology was associated with increased risk of death.