Patient Preference for Surgical Methods for Ipsilateral Breast Tumor Recurrence.

BACKGROUND: Mastectomy has been the standard surgical treatment for ipsilateral breast tumor recurrence (IBTR). Recently, there has been growing interest in repeat breast-conserving surgery (rBCS) for IBTR among breast surgeons; however, there is currently little information regarding patient preferences for surgical procedure for IBTR. The purpose of this study was to evaluate preference for surgical procedure (mastectomy vs. rBCS) among breast cancer patients who had undergone salvage surgery for IBTR. METHODS: Overall, 100 breast cancer patients who had undergone salvage surgery for IBTR were asked about their preferred surgical methods for IBTR and the reason. The association of patient preference and the reasons related to various clinical and pathological factors were assessed. RESULTS: Of the 100 respondents, only 11 patients (11%) preferred rBCS. Patients who had undergone rBCS and radiotherapy for IBTR were significantly more likely to prefer to undergo rBCS than other groups (p = 0.030). The most frequent reason for choosing rBCS was the patient's desire to minimize breast deformity and surgical wounds. CONCLUSIONS: Our study revealed that there is a low rate of patients who opt to undergo rBCS among patients who had undergone salvage surgery for IBTR. Discrepancies in perceptions regarding the surgical procedure for IBTR between patients and their surgeons may exist.

Real-world progression-free survival and overall survival of palbociclib plus endocrine therapy (ET) in Japanese patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer in the first-line or second-line setting: an observational study.

BACKGROUND: A recent large real-world study conducted in the United States reported the effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- advanced breast cancer (ABC). However, local clinical practice and available medical treatment can vary between Japan and Western countries. Thus, it is important to investigate Japanese real-world data. This observational, multicenter study (NCT05399329) reports the interim analysis of effectiveness of palbociclib plus ET as first-line or second-line treatment for HR+/HER2- ABC by estimating real-world progression-free survival (rwPFS) and overall survival (OS) in Japanese routine clinical practice. METHODS: Real-world clinical outcomes and treatment patterns of palbociclib plus ET were captured using a medical record review of patients diagnosed with HR+/HER2- ABC who had received palbociclib plus ET in the first-line or second-line treatment across 20 sites in Japan. The primary endpoint was rwPFS; secondary endpoints were OS, real-world overall response rate, real-world clinical benefit rate, and chemotherapy-free survival. RESULTS: Of the 677 eligible patients, 420 and 257 patients, respectively, had received palbociclib with ET as first-line and second-line treatments. Median rwPFS (95% confidence interval) was 24.5 months (19.9-29.4) for first-line and 14.5 months (10.2-19.0) for second-line treatment groups. Median OS was not reached in the first-line group and was 46.7 months (38.8-not estimated) for the second-line group. The 36-month OS rates for de novo metastasis, treatment-free interval (TFI) ≥ 12 months, and TFI < 12 months were 80.2% (69.1-87.7), 82.0% (70.7-89.3), and 66.0% (57.9-72.9), respectively. CONCLUSION: The addition of palbociclib to ET was effective for treating HR+/HER2- ABC in Japanese routine clinical practice.

Detection of high-risk patients resistant to CDK4/6 inhibitors with hormone receptor-positive HER2-negative advanced and metastatic breast cancer in Japan (KBCSG-TR-1316).

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve the prognosis of hormone receptor-positive HER2-negative advanced/metastatic breast cancer (HR+/HER2- mBC). However, some cancers show resistance to CDK4/6i and have a poor prognosis. The non-luminal disease score (NOLUS) was developed to predict non-luminal disease using immunohistochemical analysis. METHODS: The association between the efficacy of CDK4/6i and NOLUS was investigated by evaluating pathological and clinical data, including real-world progression-free survival (rw-PFS) and overall survival (OS). Real-world data of patients with HR+/HER2- mBC who received CDK4/6i therapy [palbociclib or abemaciclib] as first- or second-line endocrine treatments was obtained. NOLUS was calculated using the formula: NOLUS (0-100) = - 0.45 × estrogen receptor (ER) (%) - 0.28 × progesterone receptor (PR) (%) + 0.27 × Ki67(%) + 73, and the patients were divided into two groups: NOLUS-positive (≥ 51.38) and NOLUS-negative (< 51.38). RESULTS: Of the 300 patients, 28 (9.3%) were NOLUS-positive, and 272 (90.7%) were NOLUS-negative. The expression rates (%) of ER and PgR in NOLUS-positive patients were lower than those in NOLUS-negative patients (p < 0.001). Ki67 expression was higher in NOLUS-positive patients. There were statistically significant differences in prognosis (rw-PFS and OS) between the two groups. Moreover, NOLUS-negative patients showed statistically better rw-PFS with first-line therapy than second-line therapy. However, NOLUS-positive patients showed poor prognoses with both the first and second therapeutic lines, suggesting CDK4/6i inefficacy for NOLUS-positive patients. CONCLUSIONS: The efficacy and prognosis of CDK4/6i significantly differed between the NOLUS-positive and NOLUS-negative patients. This feasible method can predict patients with HR+/HER2- mBC resistant to CDK4/6i and help select a better therapeutic approach to overcome resistance.

Preferences Regarding Breast Surgery Omission Among Patients With Breast Cancer Who Receive Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Currently, several ongoing prospective studies are investigating the safety of breast surgery omission in patients with breast cancer who are exceptional responders to neoadjuvant chemotherapy. However, there is little information about the preferences of these patients regarding omission of breast surgery. PATIENTS AND METHODS: We conducted a questionnaire survey to assess preferences regarding omission of breast surgery among patients with breast cancer who had human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors and good clinical response after neoadjuvant chemotherapy. Patients' estimation of the risk of ipsilateral breast tumor recurrence (IBTR) after definitive surgery or breast surgery omission was also assessed. RESULTS: Of 93 patients, only 22 (23.7%) said they would omit breast surgery. Under the scenario of omitting breast surgery, the 5-year IBTR rate estimated by patients who said they would omit breast surgery was significantly lower (median, 10%) than the rate estimated by patients who preferred undergoing definitive surgery (median, 30%) (p=0.017). CONCLUSION: The proportion of our surveyed patients who were willing to omit breast surgery was low. Patients who said they preferred to omit breast surgery overestimated the 5-year IBTR risk.

Classification of Local Recurrence After Nipple-Sparing Mastectomy Based on Location: The Features of Nipple-Areolar Recurrence Differ from Those of Other Local Recurrences.

BACKGROUND: Little information is available about the clinical and pathologic characteristics of local recurrence (LR) after nipple-sparing mastectomy according to the locations of LR. METHODS: This study classified 99 patients into the following two groups according to the location of LR after nipple-sparing mastectomy: nipple-areolar recurrence (NAR) group and other locations of LR (oLR) group. The study evaluated whether the location of LR was associated with disease-free survival (DFS) after LR resection. RESULTS: For about half of the patients (44.4 %) with NAR, the primary cancer was estrogen receptor (ER)-negative and human epidermal growth factor receptor 2 (HER2)-positive. Conversely, in most of the patients with oLR (79.2 %), the primary cancer was ER-positive and HER2-negative. Among the LR tumors, the frequency of noninvasive carcinoma in the NAR tumors was significantly higher than in the oLR tumors (51.9 % vs 4.2 %, respectively). During a median follow-up period of 46 months, the location of LR was not associated with DFS after LR. In the NAR group, the presence or absence of LR tumor invasiveness was the only factor associated with DFS. In the oLR group, age at primary surgery was the only factor associated with DFS. CONCLUSION: This multi-institutional retrospective study demonstrated that the features of NAR, such as the characteristics of the primary and recurrent tumors and the prognostic factors after LR resection, were quite different from those of oLR.

Comparative evaluation of nuclear and histological grades as prognostic factors for invasive breast cancer.

BACKGROUND: Although tumor grade, defined by either the nuclear grade (NG) or the histological grade (HG), is widely accepted as one of the prognostic factors for breast cancer, there is a limited direct comparison between these two grading systems. The object of the current study was to compare their prognostic capabilities on the same specimen in a single institutional cohort. METHODS: We collected data from 1125 patients with breast cancer who underwent surgery at Kaizuka City Hospital between 2002 and 2016 and analyzed the prognostic capability of NG and HG in comparison with other clinicopathological factors. Pathological diagnoses were performed by a single pathologist throughout the study period. RESULTS: The median follow-up was 52.9 months. During the follow-up period, 103 distant recurrences were observed. The concordance rate of grades between NG and HG was 72.1%. The 5-year recurrence-free survival (RFS) rates for patients with NG1, NG2, and NG3 were 90.6%, 91.8%, and 82.2%, respectively, and the rates for patients with HG1, HG2, and HG3 were 92.7%, 88.6%, and 82.5%, respectively. Significant differences in RFS were noted among each grade for HG. However, this was not true for NG; a significant difference was not noted between NG1 and NG2. In terms of subtypes, both NG3 and HG3 were significantly associated with worse outcomes in patients with ER-positive/HER2-negative tumors. CONCLUSIONS: Although not a few patients exhibited discordant results between NG and HG, both NG and HG predict outcomes for breast cancer patients, but the latter might appear to be superior as a three-grade classification scale.

Fine-needle aspiration cytology for the diagnosis of solid basaloid adenoid cystic carcinoma of the breast: Its role, limitation, and perspective.

Solid basaloid adenoid cystic carcinoma (SB-AdCC) is a subtype of breast AdCC which shows more aggressive clinical behavior than other subtypes. Fine-needle aspiration (FNA) cytology is a useful diagnostic tool for breast malignancies. However, most of the diagnostic cytological characteristics of AdCC are not present in SB-AdCC and cytomorphological studies of this subtype are limited. Here, we evaluated the utility of FNA in the diagnosis of SB-AdCC of the breast. A search of the pathology archives of our institutions for FNA specimens of histologically confirmed SB-AdCC between 2012 and 2019 identified four patients with SB-AdCC of the breast. All patients were female and the average age was 60 years. Cytologically, one case was classified as malignant, two as indeterminate, and one as unsatisfactory. Smears had low to moderate cellularity. All smears showed ribbon-like material surrounding the clusters and a vertical nuclear arrangement toward the peripheral rim. Hyaline globules appeared only in one case. Cells in all cases showed an oval, angular, and spindle shape hyperchromatic nuclei with mild to severe atypia, and also dispersed naked nuclei similar to the cells of the clusters were detected in one case. In histological sections, these cytological findings were compatible with the histological findings and divergent histological differentiation was detected. Diagnosing of few cellular smears of SB-AdCC is difficult whereas the features of peripheral rim of the clusters, naked nuclei, and the divergent differentiation may be important for diagnosing SB-AdCC of the breast.

PIK3CA mutations in serum DNA are predictive of recurrence in primary breast cancer patients.

We attempted to develop a highly sensitive and specific method for the detection of circulating tumor DNA (ctDNA) using a digital PCR (dPCR) assay for PIK3CA mutations (i.e., H1047R, E545K, and E542K) in primary breast cancer patients. The sensitivity of the dPCR assay for the mutant alleles was examined using cell lines with PIK3CA mutations and proved to be 0.01 %. Serum samples were collected pre-operatively from 313 stage I-III breast cancer patients, of whom 110 were found to have PIK3CA mutant tumors. The serum samples from these patients with PIK3CA mutant tumors were subjected to the dPCR assay, and 25 (22.7 %) were found to be positive. No PIK3CA mutant ctDNA was detected in the serum samples of 50 healthy women and 30 breast cancer patients with PIK3CA non-mutant tumors. The patients with PIK3CA mutant ctDNA were dichotomized into mutant ctDNA-high (ctDNA(high)) and ctDNA-low (ctDNA(low)) groups based on the median. The ctDNA(high) patients exhibited significantly shorter recurrence-free survival (RFS; P = 0.0002) and overall survival rates (OS; P = 0.0048) compared to those exhibited by the combined ctDNA(low) patient and ctDNA-free patient group. Multivariate analysis revealed that ctDNA(high) status significantly predicted poor RFS and OS and did so independently of conventional histological parameters. These results suggest that dPCR is a highly sensitive and specific method for the detection of PIK3CA mutant ctDNA and that ctDNA(high) but not ctDNA(low) status is a significant and independent prognostic factor for primary breast cancer patients.

[A case of thyroid medullary carcinoma with multiple painful bone metastases successfully treated with strontium-89 chloride].

A 70-year-old man was diagnosed as thyroid medullary carcinoma with multiple bone metastases. He underwent total thyroidectomy and cervical lymph node dissection. After one year, the pain from his bone lesions was becoming severe. To relieve the pain, he was administered opioids and external-beam radiation therapy. However, he continued to have substantial multiple bone pain. We used combination therapy of strontium-89 chloride for the treatment of widespread multiple bone pain and external-beam radiation therapy for localized pain. That combination therapy was effective and improved the QOL of the patient. We used strontium-89 chloride four times within one year, and no serious side effects occurred during therapy. Our thoroughly investigated case suggests that strontium-89 therapy is one of the effective and safe therapies for patients with painful bone metastases of thyroid medullary carcinoma.

[Assessment of nausea and vomiting during FEC regimen for breast cancer after the novel antiemetic agent - introduction using MASCC antiemesis tool].

Chemotherapy-induced nausea and vomiting(CINV)is one of the side effects causing significant psychological and physical suffering in patients receiving chemotherapy. Because CINV often impairs patients' quality of life and leads to discontinuation of treatments, antiemetic therapy has been considered important. The MASCC Antiemesis Tool(MAT)was proposed for the assessment of acute and delayed nausea and vomiting after, we evaluated the actual situation of nausea and vomiting for Japanese patients. In a previous investigation, even conventional antiemesis therapy was a highly effective treatment during the acute phase, but the control of nausea and vomiting during the delayed phase proved difficult. Recently, a new5 -HT3 receptor blocker(palonosetron)and an NK1 receptor blocker(aprepitant) were introduced, and an effective treatment of nausea and vomiting for the delayed phase is non expected. In this examination, we evaluated the usefulness of the new antiemetic drugs(palonosetron and aprepitant)in 12 prospective patients with breast cancer(40-69 years old, median age 53 years old)for whom FEC therapy was given as an ambulant treatment using MAT. No vomiting occurred in the acute and delayed phase. Nausea during the acute phase was controlled, and was mild during the delayed phase, also. It was confirmed that the onset of acute and delayed nausea and vomiting were relieved by the newantiemetic agents compared with the previous MAT evaluation.

[A case of breast cancer with chronic renal failure successfully treated with TC therapy as adjuvant chemotherapy].

A 49-year-old pre-menopausal woman was diagnosed with left breast cancer(T2N0M0, stage II A). She was also diagnosed with chronic renal failure for the first time. We performed left breast conserving surgery and sentinel lymph node biopsy. Afterwards, we administered TC therapy(docetaxel 75mg/m / 2, cyclophosphamide 250 mg/m2)as adjuvant therapy every four weeks. No serious side effects occurred during therapy. TC therapy was a safe regimen for a patient with chronic renal failure in our case.