Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/µL for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC.

Ectopic Breast Cancer Arising within an Axillary Lymph Node.

We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis.

Systemic immunity markers are associated with clinical outcomes of atezolizumab treatment in patients with triple-negative advanced breast cancer: a retrospective multicenter observational study.

Immune checkpoint inhibitors (ICI) are reportedly efficacious against triple-negative breast cancer (TNBC) and are now recommended as first-line therapy. Systemic immunity markers, the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR), have been identified as predict ICI efficacy in patients with various cancers. We retrospectively enrolled 36 TNBC patients who received atezolizumab treatment between September 2019 and May 2021 at eight Japanese medical institutions. We evaluated systemic immunity markers, including dynamic changes in these markers, as predictors of survival benefit derived from atezolizumab treatment. Median time-to-treatment failure (TTF) and overall survival (OS) were 116 days and "not reached", respectively. Patients with low NLR at baseline and decreased NLR at the start of the second cycle (SO2nd) had significantly longer OS than those with high NLR at baseline and increased NLR (SO2nd) (log-rank P < 0.001 and log-rank P = 0.049, respectively). Multivariate analyses identified high ALC at baseline and decreased NLR (SO2nd) as independent predictive markers for longer TTF (P = 0.043 and P = 0.002, respectively), and low NLR at baseline and decreased NLR (SO2nd) as independent predictive markers for longer OS (P < 0.001 and P = 0.013, respectively). The safety profile was consistent with those of previous trials. This retrospective multicenter observational study showed the clinical efficacy and safety of atezolizumab treatment. Furthermore, systemic immunity markers, including their dynamic changes, were found to be associated with clinical outcomes of atezolizumab treatment in patients with advanced or metastatic TNBC.

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.

Dynamic Changes in Absolute Lymphocyte Counts During Eribulin Therapy Are Associated With Survival Benefit.

BACKGROUND/AIM: We investigated the usefulness of dynamic changes in absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) during eribulin therapy as predictive markers for survival benefit including post-progression survival (PPS). PATIENTS AND METHODS: We retrospectively investigated 94 advanced breast cancer (ABC) patients who underwent eribulin therapy between July 2011 and June 2020. RESULTS: The multivariate analysis showed that high baseline ALC and low NLR were independent predictive markers for overall survival (OS) (p=0.007 and p=0.011, respectively) and PPS (p=0.005 and p=0.007, respectively). Dynamic changes in ALC were also associated with OS and PPS (p=0.015, and p=0.026, respectively) and were an independent predictive marker for PPS (p=0.021). CONCLUSION: Baseline ALC and NLR and dynamic changes in ALC during eribulin therapy were significantly associated with survival benefit including PPS for patients with ABC.

Leptomeningeal Metastasis in ER + HER2- Advanced Breast Cancer Patients: A Review of the Cases in a Single Institute Over a 15-year Period.

PURPOSE: While leptomeningeal metastasis (LM) from estrogen receptor-positive, HER2-negative advanced breast cancer (ER + HER2-ABC) has a poor prognosis, the details of ER + HER2-LM are unclear. We therefore retrospectively investigated patients with LM from ER + HER2-ABC. METHODS: ER + HER2-ABC patients who received any therapy at Shizuoka Cancer Center between October 2002 and December 2017 were retrospectively analyzed. Patients with central nervous system (CNS) metastases were divided into three groups: brain metastasis (BM) only (B group); BM with LM (BL group); and LM only (L group). RESULTS: Among 369 patients, 102 developed CNS metastases: 70 (68.6%), 13 (12.8%), and 19 (18.6%) in the B, BL, and L groups, respectively. The L group showed a later onset, poorer performance status, more symptoms, and more skull metastasis than the other groups. Radiotherapy as the initial treatment was introduced to 13/13 (100%) and 15/19 (78.9%) in the BL and L groups, respectively. Subsequent systemic therapy excluding best supportive care was introduced to 5/13 (38.5%) and 5/19 (26.3%) in the BL and L groups, respectively. The median overall survival from the diagnosis of CNS lesions was 295.0, 146.0, and 99.0 days in the B, BL, and L groups, respectively, and worsening of CNS lesions was the major cause of death in the BL and L groups. Multivariate analyses showed that concurrent soft tissue metastasis (hazard ratio, 4.620) and subsequent systemic therapy (hazard ratio, 0.063) were prognostic for the L group. CONCLUSION: Management of LM from ER + HER2-ABC remains challenging, so a multimodal approach with novel systemic therapy is warranted.

Systemic immunity markers associated with lymphocytes predict the survival benefit from paclitaxel plus bevacizumab in HER2 negative advanced breast cancer.

Although paclitaxel plus bevacizumab (PB) therapy is an effective chemotherapeutic regimen for HER2-negative advanced breast cancer (ABC), predictive markers for its effectiveness remain undefined. We investigated the usefulness of systemic immunity markers associated with lymphocytes as predictive markers for PB therapy in patients with HER2-negative ABC. We retrospectively reviewed data from 114 patients with HER2-negative ABC who underwent PB therapy from November 2011 to December 2019. We calculated the absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) as representative systemic immunity markers. The time to treatment failure (TTF) and overall survival (OS) of the patients with high ALC, low NLR, and high LMR were significantly longer compared with those of the patients with low ALC, high NLR, and low LMR. A multivariable analysis revealed that high ALC, low NLR, and low PLR were independent predictors for TTF and high ALC, low NLR, and high LMR were independent predictors for OS. Systemic immunity markers were significantly associated with longer TTF and OS in patients who underwent PB therapy and may represent predictive markers for PB therapy in patients with HER2-negative ABC.

Prognostic Value of Lymphocyte-to-Monocyte Ratio for Japanese Patients With Differentiated Thyroid Cancer Treated With Sorafenib Therapy.

Background/Aim: We investigated the efficacy and safety of sorafenib in Japanese patients and the prognostic value of systemic immunity markers for predicting clinical outcomes after sorafenib therapy in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Patients and Methods: We retrospectively evaluated 26 patients with RR-DTC who underwent sorafenib therapy between July 2014 and December 2020. The systemic immunity markers were calculated from blood cell counts. Results: The median overall survival (OS) was 2,002 days, and the clinical benefit rate was 80.8%. The high lymphocyte-to-monocyte ratio (LMR) group had significantly longer OS than the low LMR group (hazard ratio=0.21; 95% confidence interval=005-0.88; log-rank p=0.019). Adverse events observed in this study were acceptable, and no new safety signals associated with sorafenib were found. Conclusion: Sorafenib therapy is efficacious and safe for Japanese patients with RR-DTC, and baseline LMR may be useful as a sorafenib therapy prognostic marker.

The Systemic Immune Markers at Diagnosis Can Predict the Survival Benefit in Advanced Breast Cancer.

Background/Aim: It has been difficult to establish prognostic markers for overall survival (OS) in patients with advanced breast cancer (ABC). Although systemic immune markers were reported as prognostic markers in several cancers, their utility in ABC remains unclear. Patients and Methods: We retrospectively analyzed 331 ABC patients, who received treatment at Fukuyama City Hospital between April 2009 and December 2020. Results: Patients with high absolute lymphocyte count (ALC), low neutrophil-to-lymphocyte ratio (NLR), and high lymphocyte-to-monocyte ratio (LMR) had significantly longer OS (p=0.025, p=0.010, and p<0.001, respectively). High ALC and high LMR were independently associated with longer OS (p=0.020 and p=0.015, respectively). High ALC was also independently associated with longer time to treatment failure (p=0.014). Conclusion: These systemic immune markers at diagnosis can predict not only a better OS but also a better TTF after first-line treatment.

De-escalated Therapy Omitting Anthracyclines for Stage I HER2-positive Breast Cancer: A Retrospective Observational Study.

BACKGROUND: It is unclear whether the de-escalated therapy that omits anthracycline-based chemotherapy is as beneficial as standard therapy for patients with stage I human epidermal growth factor receptor 2-positive (HER2+) early breast cancer. PATIENTS AND METHODS: We retrospectively investigated 95 patients with pathological stage I HER2+ early breast cancer who underwent adjuvant treatment from April 2009 to December 2018. RESULTS: We assessed 45 patients who underwent standard therapy containing anthracyclines, 35 patients who underwent paclitaxel plus trastuzumab (P+TRA group), and 15 patients who underwent trastuzumab monotherapy or no adjuvant therapy; the 5-year invasive disease-free survival rates were 97.8%, 92.9%, and 93.3%, respectively (p=0.255). Adverse events were significantly less frequent in the P+TRA group than that in the standard therapy group. CONCLUSION: In a real-world setting, de-escalated therapy without anthracyclines demonstrated excellent outcomes similar to the standard therapy containing anthracyclines as well as lower adverse events.

Bevacizumab as First-line Treatment for HER2-negative Advanced Breast Cancer: Paclitaxel plus Bevacizumab Versus Other Chemotherapy.

BACKGROUND: The efficacy of paclitaxel and bevacizumab (PB) compared with other chemotherapies in patients with human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer is unclear. PATIENTS AND METHODS: We retrospectively investigated 301 patients with HER2- ABC who received first-line chemotherapy from January 2011 to December 2016. RESULTS: We included 114 patients who received PB and 187 patients who received other chemotherapies. After propensity score matching, the PB group showed a significantly superior overall response rate (77.8% vs. 38.9%, p<0.0001) and median time to treatment failure (7.3 vs. 5.9 months, p=0.035). In subgroup analyses, PB improved the median overall survival of patients with pleural lesions or pulmonary lymphangiopathy (not reached vs. 18.9 months, p=0.037), and of patients with three or more metastatic sites without liver metastases, (48.0 vs. 27.3 months, p=0.015). CONCLUSION: Compared with conventional chemotherapy, PB improved the overall response rate and time to treatment failure in patients with HER2- advanced breast cancer and improved overall survival in some patient subgroups.

Is the presence of edema and necrosis on T2WI pretreatment breast MRI the key to predict pCR of triple negative breast cancer?

PURPOSE: Given that a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is an important prognostic factor, evaluating pretreatment imaging findings is important. Outcomes for triple negative breast cancer (TNBC) vary with the histological classification, indicating that this classification is clinically significant. In this study, we focus on the most common histological subtype of TNBC, invasive carcinoma of no special type (NST), to evaluate whether intramammary edema (intra-E) and intratumoral necrosis (intra-N) on T2-weighted magnetic resonance imaging (T2WI) is a useful predictor of pCR. METHOD: We retrospectively included patients with biopsy-diagnosed TNBC-NST who received NAC between January 2014 and December 2017. Intra-E and intra-N were evaluated on T2WI before NAC. We grouped intra-E into no edema, peritumoral edema, prepectoral edema, and subcutaneous edema, and we defined intra-N as water-like signal intensity without enhancement on T2WI. We also evaluated tumor size, Ki-67 expression, and histological/nuclear grade, as well as their correlation with intra-E and intra-N. RESULTS: Fifty-seven patients with TNBC-NST were enrolled. There was no correlation with the rate of pCR and the presence of either intra-E or intra-N before NAC. Only intra-E and tumor size showed a positive correlation. CONCLUSIONS: In patients with TNBC-NST, intra-E and intra-N did not correlate with pCR, but intra-E did positively correlate with tumor size. NST may exhibit a greater response to NAC, regardless of whether intra-E or intra-N is present or not on the pretreatment MRI. KEY POINTS: • Pathological complete response in TNBC-NST had no correlation with intramammary edema or intratumoral necrosis. • NAC may be justified in TNBC-NST even in the presence of edema or necrosis. • The extension of edema correlated with tumor size of TNBC-NST.

Imaging features of breast cancer with marked hemosiderin deposition: A case report.

A 63-year-old woman was referred to our hospital for breast cancer treatment. She had a large HER2-positive breast tumor on her left breast, and received neoadjuvant chemotherapy. After treatment, a shrunk spiculated mass with calcification-like high density was detected on mammography, and MRI revealed a large strong susceptibility artifact. Surgical specimen analysis attributed these imaging features to a large marked hemosiderin deposition. This case is herein reported due to its rarity and to the importance of acknowledging that this large marked hemosiderin depositions can present as a calcification-like high density on mammography and shows large susceptibility artifact on MRI imaging.