Purpose
To assess the diagnostic performance of sentinel lymph node (SLN) biopsy using the indocyanine green (ICG) fluorescence method compared with that using the blue dye method, a prospective ...multicenter study was performed.
Methods
Patients with T1–3 primary breast cancer without clinical lymph node involvement were included in this study. ICG as a fluorescence-emitting source and indigo carmine as blue dye were injected into the subareolar area. Extracted lymph nodes were examined to identify the first, second, and other SLNs. The identified nodes were classified according to the ICG fluorescence signal and blue dye uptake.
Results
Ninety-nine eligible patients were included in this study. The ICG fluorescence method identified an average of 3.4 SLNs (range, 1–8) in 98 of 99 patients (detection rate, 99 %). The number of lymph nodes identified by the fluorescence method was significantly higher than that identified by the blue dye method (
p
< 0.001). SLN involvement was identified in 20 % (20 of 99) of patients, all of whom tested positive for the first SLN. In 16 patients, complete axillary lymph node dissection (ALND) was performed. In 25 % (4 of 16) of these patients, axillary metastases were identified; however, no axillary involvement was found in 8 patients with only one involved node, which was isolated as the first SLN.
Conclusions
High rate of SLN detection was achieved using the ICG fluorescence method. The first SLN identified by fluorescence imaging provides an exact indication of the axillary status. Therefore, the ICG fluorescence method provides precise information required to avoid unnecessary ALND.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Although peripheral blood-based parameters (PBBPs) are reported as prognostic indicators in patients with breast cancers, their utility has not been studied in human epidermal growth factor receptor ...2 (HER2)-positive advanced breast cancer (ABC). Tumor-infiltrating lymphocytes (TILs) might be a predictive factor in patients with HER2-positive ABC treated with pertuzumab and trastuzumab (PT) plus docetaxel. We aimed to evaluate whether PBBPs could have predictive value in HER2-positive ABC treated with pertuzumab and trastuzumab (PT) combined with eribulin (ERI) or nab-paclitaxel (Nab-PTX).
Data from 51 patients included in two single-arm, phase II trials were included in this retrospective-prospective study; the ERI + PT (N = 30) and Nab-PTX + PT (N = 21) combinations were registered under clinical trials number UMIN000012375 and UMIN000006838, respectively. We assessed PBBPs using prospectively collected data and investigated the association with progression-free survival (PFS); we evaluated absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The cutoff values for ALC, NLR, and PLR were set at 1000 or 1500 cells/μL, 2, and 250, respectively.
PFS was significantly improved in patients with ALC ≥1500/μL compared to those with ALC 1000-, <1500/μL or ALC < 1000/μL (P = 0.0106). High baseline ALC was significantly associated with improved PFS (≥1500/μL; hazard ratio HR: 0.3715; 95% confidence interval CI: 0.1735-0.7955; P = 0.0108). In contrast, improved PFS was not significantly associated with NLR or PLR. Improved PFS in patients with ALC ≥1500/μL was observed irrespective of visceral metastasis or chemotherapy regimen.
Our results showed that baseline ALC was a predictive factor for PFS in HER2-positive ABC treated with PT irrespective of combined chemotherapy regimen. Anti-tumor effects might be mediated not only by the tumor microenvironment, but also by systemic peripheral circulating lymphocytes. Baseline systemic parameters such as peripheral lymphocyte count might be beneficial in addition to disease extent for predicting the efficacy of PT treatment.
UMIN000012375 , registration date: 21NOV2013, and UMIN000006838 , registration date: 6DEC2011.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
We investigated the barriers to and promoters of taking
BRCA
testing, after the start of national healthcare insurance coverage for non-metastatic breast cancer patients in Japan.
Patients ...and Methods
This was a multi-center, retrospective, cohort study. We included stage 0 to III breast cancer patients who were diagnosed and met the criteria for insurance coverage of
BRCA
testing between April 2020 and December 2021. We examined the association between
BRCA
testing and possible exposures: breast cancer diagnosis at 45 years or younger, triple-negative breast cancer (TNBC) diagnosis at the age of 60 or younger, two or more primary breast cancers, family history of breast cancer or ovarian cancer in the third degree of relatives, male breast cancer, medical expense limits, and parity. We used logistic regression analysis.
Results
We included 222 patients and 123 (55.4%) of them underwent the test. In univariate analysis, a family history of ovarian cancer (odds ratio (OR) 10.59; 95% CI 1.35–82.96,
p
= 0.025), diagnosis of breast cancer at the age of 45 or younger (OR 2.78; 95% CI 1.52–5.14,
p
= 0.0009), and diagnosis of TNBC at the age of 60 or younger (OR 3.95; 95% CI 1.55–10.07,
p
= 0.004) were associated with taking the test. After multivariate logistic regression analysis, a family history of ovarian cancer (adjusted OR 12.80; 95% CI 1.51–108.80,
p
= 0.0195), diagnosis of breast cancer at the age of 45 or younger (adjusted OR 4.43; 95% CI 1.98–9.90,
p
= 0.0003), and TNBC at the age of 60 or younger (adjusted OR 5.28; 95% CI 1.90–14.66,
p
= 0.0014) were consistently associated.
Conclusion
For non-metastatic breast cancer patients whose
BRCA
testing is covered by insurance, costs would no longer be a definite barrier. Physicians should keep in mind that a family history of ovarian cancer, breast cancer diagnosis at 45 years of age or younger and TNBC diagnosis at 60 years of age or younger are strong promoters.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study aimed to examine whether the incidence of febrile neutropenia (FN) during perioperative chemotherapy for breast cancer increased in patients with periodontal disease who had received prior ...dental treatment.
This retrospective cohort study conducted at a single tertiary care center included patients diagnosed with clinical stages I-III of breast cancer and had started neoadjuvant or adjuvant intravenous chemotherapy between July 2015 and November 2021. The exposure was periodontal disease (probing depth ≥6 mm) diagnosed by dentists before the start of chemotherapy. Almost all the patients received dental treatment and oral care before initiating chemotherapy. The primary outcome was FN incidence during chemotherapy. We used a multivariable logistic regression model adjusted for age, diabetes mellitus, chemotherapy regimen, and the mean relative dose intensity.
Based on the eligibility criteria of this study, 141 women were included. The incidence of FN in the periodontal group (probing depth ≥6 mm) and control group (probing depth <6 mm) was 36.4% and 25.9%, respectively. The crude odds ratio (OR) for FN incidence was 1.63 (95% confidence interval CI, 0.71-3.74; P = 0.24), and the adjusted OR was 1.52 (95% CI, 0.62-3.73; P = 0.36). Conclusions: Occurrence of FN during perioperative chemotherapy for breast cancer is not a concern in patients undergoing dental treatment for periodontal disease before or during chemotherapy.
Radiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic ...breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy. Patients received 8 Gy single fraction RT for bone metastasis on day 0. Nivolumab was administered on day 1 for each 14-day cycle. In cohort A, endocrine therapy was administered. The primary endpoint was the objective response rate (ORR) of the unirradiated lesions. Cohorts A and B consisted of 18 and 10 patients, respectively. The ORR was 11% (90% CI 4-29%) in cohort A and 0% in cohort B. Disease control rates were 39% (90% CI 23-58%) and 0%. Median progression-free survival was 4.1 months (95% CI 2.1-6.1 months) and 2.0 months (95% CI 1.2-3.7 months). One patient in cohort B experienced a grade 3 adverse event. Palliative RT combined with nivolumab was safe and showed modest anti-tumor activity in cohort A. Further investigations to enhance the anti-tumor effect of endocrine therapy combined with RT plus immune checkpoint blockade are warranted.Trial registration number and date of registration UMIN: UMIN000026046, February 8, 2017; ClinicalTrials.gov: NCT03430479, February 13, 2018; Date of the first registration: June 22, 2017.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in ...patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting.
Methods
This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model.
Results
Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07–2.68) and 1.75 (95% CI, 1.28–2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (
n
= 98) was 2.56 years (95% CI 2.27–2.74), while it was 2.87 years (95% CI 2.20–4.32) for those who avoided anthracycline and taxane as first- and second-line (
n
= 48) (adjusted HR, 1.20; 95% CI 0.70–2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14–2.75) and 2.91 years (95% CI 2.61–4.32) for those aged < 65 and ≥ 65 years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56–1.46).
Conclusions
Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting.
Trial registration
This study is registered with Clinical Trials.gov (NCT 02,551,263).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background:
Clinical studies have shown that palbociclib improves progression-free survival in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) patients with ...advanced breast cancer (ABC). However, there are insufficient data on its use in a real-world setting in Japan. The aim of this study was to investigate the effectiveness, predictive factors, and safety of palbociclib among Japanese patients in routine clinical practice.
Methods:
Between December 1, 2017, and April 30, 2019, we recruited patients from 9 hospitals and retrospectively evaluated the data on HR+/HER2− patients with ABC who received palbociclib for at least 1 week. The correlation between time-to-treatment discontinuation (TTD) and clinical background was investigated via univariate and multivariate analyses using Cox hazards models.
Results:
A total of 177 women were available for analysis. Of these patients, 58 (33%) patients were treated with palbociclib with an aromatase inhibitor and 117 (66%) patients were treated with palbociclib and a selective estrogen receptor degrader. Approximately three-fourths of the patients (n = 130, 73%) received palbociclib as third- or later-line therapy. One-third of the patients had 3 or more metastatic sites (n = 59, 33%), and one-third of the patients had liver metastasis (n = 59, 33%). The median follow-up duration at the time of data cutoff was 8.9 months, the median TTD was 6.3 months, and the median overall survival was not reached. Liver metastasis (hazard ratio HR: 1.54 95% confidence interval {CI}: 1.03-2.27), high serum lactate dehydrogenase (LDH) level (>300 U/L) (HR: 2.58 95% CI: 1.49-4.26), and high neutrophil-to-lymphocyte ratio (NLR) (⩾3.0) (HR: 1.76 95% CI: 1.13-2.69) were significantly associated with shorter TTD. The most common hematologic adverse event was neutropenia, which occurred in 93% of the patients.
Conclusion:
Based on the results of the pivotal phase 3 trials, the median TTD recorded in this study was shorter than expected. Our results suggest that liver metastasis, serum LDH level, and NLR may be predictive factors for HR+/HER2− ABC treatment outcomes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Background
Endocrine treatment-related adverse events have a strong impact on patients’ quality of life and sometimes result in treatment discontinuation. Since joint symptoms are the most frequently ...recognized side effect of aromatase inhibitors, evaluation of associated risk factors may yield significant findings.
Patients and methods
A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers for assessment of patient-reported outcomes (PROs) in this prospective cohort study (SAVS-JP, UMIN000002455). Patients completed the self-report questionnaire at baseline and after 3, 6, 9, and 12 months of treatment for evaluation of frequency of treatment-related joint symptoms (arthralgia, decrease in range of joint motion, and joint stiffness).
Results
We obtained PROs from 362 patients (92.6 %) at baseline and at one or more subsequent points. New or worsening from baseline of joint symptoms were reported by 260 patients (71.8 %). More than 90 % of the symptoms were mild or moderate and nearly 80 % had occurred by 6 months. Multivariate analysis showed that a short time span after menopause odds ratio (OR) 0.95, 95 % confidence interval (CI) 0.90–0.99;
P
= 0.02 and adjuvant chemotherapy (OR 2.29, 95 % CI 1.06–4.95;
P
= 0.03) were significant independent risk factors for joint symptoms. No significant relationships between body mass index (BMI) and joint symptoms were identified. Eighteen patients discontinued treatment during the 1st year and eight of them reported joint symptoms.
Conclusion
Taking into consideration that PROs may yield higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials, we found that a short time span after menopause and use of adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These findings might prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors in postmenopausal Japanese women.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Bone metastasis (BM) is important for studying systemic spread of breast cancer. It often causes skeletal-related events (SREs) that worsen quality of life. We investigated the prevalence ...and risk factors for BM and SRE using a dataset from the Breast Oncology Research Network (BORN) in Japan.
Patients and methods
We collected data on primary breast cancer patients with node-positive or node-negative disease at intermediate to high risk of recurrence. The risk factors affecting the BM-free rate, SRE-free rate and overall survival were analyzed by using the Cox proportional hazard model.
Results
Data of 1,779 patients who were diagnosed with breast cancer during 2003–2005 were collected from the BORN and 1,708 cases were used for analysis. The median follow-up duration was 5.71 years. BM developed in 193 cases (11.3 %) and the BM-free rate at 5 years was 89.2 %. The annual hazard ratio of BM development differs remarkably according to the tumor subtype. SREs occurred in 133 (68.9 %) out of 193 patients and the SRE-free rate at 5 years was 92.6 %. In the multivariate analysis, clinical stage (
P
< 0.0001), number of lymph node (LN) metastases (
P
= 0.0029), tumor subtype (
P
= 0.034) and progesterone receptor status (
P
= 0.038) were independently significant risk factors for BM-free rate, but only clinical stage (
P
< 0.0001) and number of LN metastases (
P
= 0.0004) significantly correlated with SRE-free rate.
Conclusions
This retrospective study clarifies the prevalence and risk factors for BM and SRE in Japanese breast cancer patients. Our results show the importance of considering subtype in the care of BM and SRE.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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