Four types of ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery: classification of IBTR based on precise pathological examination.

We classified ipsilateral breast tumor recurrences (IBTRs) based on strict pathological rules. Ninety-six women who were surgically treated for IBTR were included. IBTRs were classified according to their origins and were distinguished based on strict pathological rules: relationship between the IBTR and the primary lumpectomy scar, surgical margin status of the primary cancer, and the presence of in situ lesions of IBTR. The prognosis of these subgroups were compared to that of new primary tumors (NP) in the narrow sense (NPn) that occurred far from the scar. Distant-disease free survival of IBTR that occurred close to the scar with in situ lesions and a negative surgical margin of the primary cancer (NP occurred close to the scar, NPcs) was similar to that of NPn. In contrast, IBTR that occurred close to the scar without in situ lesions (true recurrence (TR) that arose from residual invasive carcinoma foci, TRinv) had significantly poorer prognosis than NPn. IBTR that occurred close to the scar with in situ lesions and a positive surgical margin of the primary cancer (TR arising from a residual in situ lesion, TRis) had more late recurrences than NPcs. Precise pathological examinations indicated four distinct IBTR subtypes with different characteristics.

Incidence and prediction of invasive disease and nodal metastasis in preoperatively diagnosed ductal carcinoma in situ.

For breast cancer patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS), sentinel lymph node (SN) biopsy has been proposed as an axillary staging procedure in selected patients with a higher likelihood of having occult invasive lesions. With detailed histological examination of primary tumors and molecular whole-node analysis of SNs, we aimed to validate whether this selective application accurately identifies patients with SN metastasis. The subjects were 336 patients with a preoperative needle-biopsy diagnosis of DCIS who underwent SN biopsy using the one-step nucleic acid amplification assay in the period 2009-2011. The incidence and preoperative predictors of upstaging to invasive disease on final pathology and SN metastasis, and their correlation, were investigated. Of the 336 patients, 113 (33.6%) had invasive disease, and 6 (1.8%) and 17 (5.0%) had macro- and micrometastasis in axillary nodes respectively. Of the 113 patients with invasive disease, 4 (3.5%) and 9 (8.0%) had macro- and micrometastasis. Predictors of invasive disease included palpability, mammographic mass, and calcifications (spread >20 mm), and intraductal solid structure, but no predictor was found for SN metastasis. Therefore, even though occult invasive disease was found at final pathology, most of the patients had no metastasis or only micrometastasis in axillary nodes. Predictors of invasive disease and SN metastasis were not completely consistent, so the selective SN biopsy for patients with a higher risk of invasive disease may not accurately identify those with SN metastasis. More accurate application of SN biopsy is required for patients with a preoperative diagnosis of DCIS.

Time trend of breast cancer-related lymphedema according to body mass index.

PURPOSE: To clarify how body mass index (BMI) affects the development and temporal trend of breast cancer-related lymphedema (BCRL). METHODS: This is a prospective study in which patients with operable breast cancer were registered in a single institute between November 2009 and July 2010. The incidence of lymphedema at 1, 3, and 5 years after surgery was assessed according to BMI, and the trend of newly developed BCRL was examined. Obesity was defined as BMI ≥25 in accordance with the Japan Society for the Study of Obesity. RESULTS: A total of 368 patients were included in this study. The multivariate analysis of the whole population showed that high BMI, axillary dissection, and radiotherapy remained as risk factors for BCRL. Patients with high BMI showed a significantly higher incidence of new lymphedema than those with low BMI at 1 year (p < 00.001) regardless of axillary procedures (39.1 % vs 16.3 % for axillary dissection; 15.6 % vs 1.5 % for sentinel lymph node biopsy) but not at 3 and 5 years. Once BCRL developed, patients with high BMI showed slow recovery and 50.0 % of the patients retained edema at 5 years while patients with low BMI showed rapid recovery and 26.7 % retained after 3 years (p = 0.04). CONCLUSION: The preoperative BMI affected the incidence and temporal trend of BCRL regardless of axillary procedures or radiotherapy. Patients with high BMI should be given appropriate information about BCRL before surgery with careful follow-up for BCRL after treatment.

Detection of occult invasion in ductal carcinoma in situ of the breast with sentinel node metastasis.

By definition, ductal carcinoma in situ (DCIS) - pre-invasive breast cancer - does not metastasize to the lymph nodes. However, since the introduction of molecular whole-node analysis using the one-step nucleic acid amplification assay for sentinel node (SN) biopsies, the number of patients with DCIS and SN metastasis has increased. The pathogenesis and clinical management of DCIS with SN metastasis remain controversial. In this case-control study, in order to elucidate the pathogenesis of SN metastasis in DCIS, we compared occult invasions between the SN-positive and SN-negative DCIS and investigated predictive factors of occult invasion. The subjects were 24 patients selected from 285 patients with a routine postoperative diagnosis of DCIS who had undergone SN biopsy using the one-step nucleic acid amplification whole-node assay between 2009 and 2011. Of these 24 patients, 12 were SN-positive, and 12 were SN-negative. The 12 SN-negative patients make up the control group and were selected from the 273 SN-negative patients based on patient characteristics. All paraffin blocks of the primary tumor from each patient were step-sectioned with 500-µm intervals until the block was exhausted and histopathologically examined. We analyzed 1830 step-sectioned slides and found occult invasions were more frequent in the SN-positive group (7/12, 58.3%) than in the SN-negative group (3/12, 25.0%). All occult invasions were <5 mm. There was no correlation between occult invasion and SN tumor burden, non-SN metastasis, or patient characteristics. Our results suggest true metastasis from occult invasion may be a potent pathogenesis indicating nodal metastasis in postoperatively diagnosed DCIS. Patient follow-up is required to elucidate the prognostic impact of nodal metastasis and occult invasion.

Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer: a comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology.

BACKGROUND: Conventional histopathological examination is limited in measuring accurate total metastatic volume in a lymph node. Recently, a molecular-based procedure to detect lymph node metastases, one-step nucleic acid amplification (OSNA) assay, has been developed. OSNA assay can assess a whole lymph node and yields semiquantitative results. The authors compared the performance in intraoperative detection of sentinel lymph node metastases with OSNA assay using a whole lymph node versus routine frozen section (FS) histology with a 2 mm-sectioned lymph node. METHODS: Subjects comprised 531 consecutive patients diagnosed with OSNA assay and 618 consecutive patients diagnosed with FS histological examination. The authors compared the sentinel lymph node-positive rate between the OSNA and FS cohorts, and investigated characteristics of patients for whom OSNA could detect metastases but FS could not. OSNA (+) was defined as micrometastasis, and OSNA (++) and (+I) were defined as macrometastasis. RESULTS: OSNA assay detected more cases of sentinel lymph node metastases than FS histology (OSNA 121 of 531, 22.8% vs FS 109 of 618, 17.6%; P = .036), particularly micrometastases (46 of 531, 8.7% vs 28 of 618, 4.5%; P = .0064). There was no difference in macrometastasis detection between OSNA and FS (75 of 531, 14.1% vs 81 of 618, 13.1%; P = .68). OSNA detected more metastases than FS in postmenopausal patients (77 of 302, 25.5% vs 43 of 351, 12.3%; P < .0001), and in tumors without fat invasion (23 of 156, 14.7% vs 6 of 151, 4.0%; P = .012) or lymphovascular invasion (67 of 395, 17.0% vs 45 of 458, 9.8%; P = .042). CONCLUSIONS: Intraoperative OSNA assay detects more sentinel lymph node metastases, particularly micrometastases, than does FS histology. OSNA assay can also detect more metastases in postmenopausal patients or from less aggressive primary tumors compared with FS histology.

MEK inhibition preferentially suppresses anchorage-independent growth in osteosarcoma cells and decreases tumors in vivo.

Osteosarcoma is the most common high-grade malignancy of bone, and novel therapeutic options are urgently required. Previously, we developed mouse osteosarcoma AXT cells that can proliferate both under adherent and nonadherent conditions. Based on metabolite levels, nonadherent conditions were more similar to the in vivo environment than adherent conditions. A drug screen identified MEK inhibitors, including trametinib, that preferentially decreased the viability of nonadherent AXT cells. Trametinib inhibited the cell cycle and induced apoptosis in AXT cells, and both effects were stronger under nonadherent conditions. Trametinib also potently decreased viability in U2OS cells, but its effects were less prominent in MG63 or Saos2 cells. By contrast, MG63 and Saos2 cells were more sensitive to PI3K inhibition than AXT or U2OS cells. Notably, the combination of MAPK/ERK kinase (MEK) and PI3K inhibition synergistically decreased viability in U2OS and AXT cells, but this effect was less pronounced in MG63 or Saos2 cells. Therefore, signal dependence for cell survival and crosstalk between MEK-ERK and PI3K-AKT pathways in osteosarcoma are cell context-dependent. The activation status of other kinases including CREB varied in a cell context-dependent manner, which might determine the response to MEK inhibition. A single dose of trametinib was sufficient to decrease the size of the primary tumor and circulating tumor cells in vivo. Moreover, combined administration of trametinib and rapamycin or conventional anticancer drugs further increased antitumor activity. Thus, given optimal biomarkers for predicting its effects, trametinib holds therapeutic potential for the treatment of osteosarcoma.

Repeated instruction on inhalation technique improves adherence to the therapeutic regimen in asthma.

BACKGROUND: Adherence to inhalation therapy is a critical determinant of the success of asthma management. Reasons for nonadherence have been well studied, but reasons for good adherence are poorly understood. Understanding the mechanisms of adherence to inhalation therapy is important in developing strategies to promote adherence. The objective of this study was to assess the factors and mechanisms that contribute to and the clinical outcomes relating to adherence to inhalation therapy. METHODS: The factors and outcomes related to adherence to inhalation therapy were examined cross-sectionally in 176 adults with asthma using a self-reported adherence questionnaire that consisted of four items dealing with the use of inhaled controller medications. A 5-point Likert scale was used for the responses to each item. Adherence was assessed based on the overall mean adherence score. RESULTS: Of the 176 patients who were potential participants, 146 (83%) responded with usable information. Significant factors associated with the overall mean adherence score were older age (r = .18, p = .032) and receiving repeated instruction on inhalation techniques (p = .0016). Of the 146 respondents, 25 (17.1%) patients were given repeated verbal instruction or demonstrations of inhalation technique by a respiratory physician. On logistic regression analysis, good adherence to inhalation therapy was significantly related to the receiving of repeated instruction on inhalation technique, with an odds ratio of 2.90 (95% confidence interval 1.07-7.88; p = .037). Furthermore, less intentional nonadherent behavior was reported in patients with repeated instruction on inhalation technique compared to those without it. A significant correlation was found between the overall mean adherence score and the frequency of asthma exacerbations (r = -.19, p = .021), emergency room visits (r = -.19, p = .042), and the health-related quality of life score (St. George's Respiratory Questionnaire: Total, r = -.22, p = .024; Symptoms, r = -.21, p = .022; Impacts, r = -.20, p = .035). CONCLUSIONS: Repeated instruction on inhalation techniques may contribute to adherence to inhalation therapy through decreasing intentional nonadherence. Furthermore, good adherence to the therapeutic regimen may offer good asthma-related outcomes.

Ductal carcinoma in situ and sentinel lymph node metastasis in breast cancer.

BACKGROUND: The impact of sentinel lymph node biopsy on breast cancer mimicking ductal carcinoma in situ (DCIS) is a matter of debate. METHODS: We studied the rate of occurrence of sentinel lymph node metastasis in 255 breast cancer patients with pure DCIS showing no invasive components on routine pathological examination. We compared this to the rate of occurrence in 177 patients with predominant intraductal-component (IDC) breast cancers containing invasive foci equal to or less than 0.5 cm in size. RESULTS: Most of the clinical and pathological baseline characteristics were the same between the two groups. However, peritumoral lymphatic permeation occurred less often in the pure DCIS group than in the IDC-predominant invasive-lesion group (1.2% vs. 6.8%, p = 0.002). One patient (0.39%) with pure DCIS had two sentinel lymph nodes positive for metastasis. This rate was significantly lower than that in patients with IDC-predominant invasive lesions (6.2%; p < 0.001). CONCLUSIONS: Because the rate of sentinel lymph node metastasis in pure DCIS is very low, sentinel lymph node biopsy can safely be omitted.

Invasive carcinoma of the breast accompanied by coarse calcification.

OBJECTIVE: We describe the case of a woman with a left breast mass. At mammography, the mass was shown to be irregular and accompanied by coarse calcification. Core needle biopsy revealed invasive carcinoma and a mastectomy was performed. Histopathology showed fibrosis with partial hyalinization eccentrically placed within the tumor with a large area of calcification at the core. CONCLUSION: Benign calcifications within a breast mass are not diagnostic of a benign process if the imaging characteristics of the mass are suspicious.

Altered lymphatic drainage patterns in re-operative sentinel lymph node biopsy for ipsilateral breast tumor recurrence.

BACKGROUND: This study aimed to evaluate the impact of previous local treatment on lymphatic drainage patterns in ipsilateral breast tumor recurrence (IBTR) based on our data on re-operative sentinel lymph node biopsy (re-SLNB) for IBTR. METHODS: Between April 2005 and December 2016, re-SLNB using lymphoscintigraphy with Tc-99 m phytate was performed in 136 patients with cN0 IBTR. Patients were categorized into two groups: the AX group included 55 patients with previous axillary lymph node dissection; the non-AX group included 69 patients with previous SLNB and 12 patients with no axillary surgery. The whole breast irradiation (RT) after initial surgery had performed in 17 patients in the AX group and 27 patients in the non-AX group. RESULTS: Lymphatic drainage was visualized in 80% of the AX group and 95% of the non-AX group (P < 0.01). The visualization rate of lymphatic drainage was associated with the number of removed lymph nodes in prior surgery. In the non-AX group, lymphatic drainage was visualized in 96% of patients without RT and 93% with RT. Lymphatic drainage was observed at the ipsilateral axilla in 98% of patients without RT and in 64% with RT (P < 0.0001). Aberrant drainage was significantly more common in patients with RT than without RT (60% vs. 19%, P < 0.001); it was observed mostly to the contralateral axilla (52% vs. 2%, P < 0.0001). In the AX group, patients with previous RT showed decreased lymphatic drainage to the ipsilateral axilla compared to those without RT (29% vs. 63%, P < 0.05) and increased aberrant drainage to the contralateral axilla (64% vs. 5%, P < 0.0001). CONCLUSION: Lymphatic drainage patterns altered in re-SLNB in patients with IBTR and previous ALND and RT were associated with alterations in lymphatic drainage patterns.

Epirubicin and cyclophosphamide followed by docetaxel as primary systemic chemotherapy in locally advanced breast cancer.

BACKGROUND: The aim of this study was to evaluate the activity and toxicity of epirubicin and cyclophosphamide (EC) followed by docetaxel as primary systemic chemotherapy (PST) in locally advanced breast cancer. PATIENTS AND METHODS: In this phase II trial, 46 patients with locally advanced breast cancer (T > 3 cm or N > 1) received epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for four cycles, followed by docetaxel (70 mg/m2) every 3 weeks for four cycles. Primary endpoints were pathological and objective response in the breast and axilla, and toxicities. RESULTS: The clinical response rate was 80.4% (95% confidence interval, 68.9-91.9%). Pathological response evaluation revealed 6 complete responses (CR: 13.0%). Patients with ER-negative tumors had a significantly higher rate of pathological CR than the others (33.3% vs. 3.2%; p = 0.0105). Febrile neutropenia occurred in 4 patients (8.7%). CONCLUSION: EC followed by docetaxel is an active and well-tolerated treatment as PST for locally advanced breast cancer.

Ultrasonographically guided 18-gauge automated core needle breast biopsy with post-fire needle position verification (PNPV).

BACKGROUND: Percutaneous imaging-guided core needle biopsy (CNB) is being used increasingly as an alternative to surgical biopsy for the diagnosis of breast lesions that are suspicious or highly suggestive of malignancy. The purpose of this study was to evaluate ultrasonographically (US) guided 18-gauge automated CNB with post-fire needle position verification (PNPV) in the assessment of US visible breast lesions. METHODS: Biopsy of 235 US visible breast lesions was performed using US-guided 18-gauge core needles (18-GCN). After firing the biopsy needle, an image was obtained in the orthogonal plane to confirm the precise post-fire position of the needle track before removing the needle. Needle core diagnoses were compared with surgical diagnoses in 235 lesions subsequently surgically excised. RESULTS: The median size of the lesions was 14 mm (range, 5-60 mm). Agreement between needle core and surgical diagnoses in the 235 lesions was 92% including 192 cancers, 28 benign lesions, and 3 high-risk lesions. In the remaining 12 discordant lesions, 4 were high-risk lesions and 8 were benign lesions. In all 8 benign lesions, imaging-histological discordance was present. The sensitivity of US guided 18-GCNB for breast cancer was 96% (199 of 207). In 71% (167/235) of the cases only one core with PNPV was made. No complications occurred. CONCLUSION: US-guided 18-GCNB for sonographically-demonstrated discrete mass lesions with PNPV is an accurate core needle biopsy technique of breast cancer. During the course of tissue sampling, evaluating the post-fire needle tip position by obtaining an orthogonal view with ultrasonographic guidance is the key to predicting the yield regardless of the size of the needle or the number of core samples.

The combination of epirubicin plus docetaxel as neoadjuvant chemotherapy in locally-advanced breast cancer.

BACKGROUND: The purpose of this study was to evaluate the activity and toxicity of epirubicin plus docetaxel as neoadjuvant chemotherapy for locally advanced breast cancer. PATIENTS AND METHODS: In this single-center, phase II trial, twenty-one patients with locally advanced breast cancer (T>3 cm or N>1) received epirubicin (70 mg/m2) and docetaxel (60 mg/m2) on Day 1 of each cycle for up to 6 cycles. RESULTS: Clinically complete responses (CR) were observed in 5 patients and partial responses were observed in 14 patients. The clinical response rate was 90.5% (95% confidence interval, 78.0-99.9). Eleven patients (52.4%) underwent breast conserving surgery. Pathological response evaluation revealed 2 CR (9.5%). Grade 4 neutropenia was recorded in 81.0% of the patients and febrile neutropenia occurred in 1 patient. CONCLUSION: The combination of epirubicin plus docetaxel was an active and well-tolerated treatment for locally-advanced breast cancer.

Long-term prognoses and outcomes of axillary lymph node recurrence in 2,578 sentinel lymph node-negative patients for whom axillary lymph node dissection was omitted: results from one Japanese hospital.

BACKGROUND: Axillary dissection omission for sentinel lymph node-negative patients has been a practice at Cancer Institute Hospital, Japanese Foundation for Cancer Research since 2003. We examined the long-term results of omission of axillary dissection in sentinel lymph node-negative patients treated at our hospital, as well as their axillary lymph node recurrence characteristics and outcomes. METHODS: Our study included 2,578 patients with cTis or T1-T3N0M0 primary breast cancer for whom dissection was omitted because they were sentinel lymph node negative. The median observation period was 75 months. RESULTS: In sentinel lymph node-negative patients for whom dissection was omitted, the rates of axillary lymph node recurrence, distant recurrence, and breast cancer mortality were 0.9, 2, and 1 %, respectively. Eighteen patients underwent additional dissection if axillary lymph node recurrence was observed at the first recurrence. Four triple-negative (TN) patients experienced distant recurrence after additional dissection. All four patients were administered anticancer agents after axillary lymph node recurrence and experienced recurrence within 1 year of additional dissection. The axillary lymph node recurrence rate was 0.8 % for luminal and 4.5 % for TN subtypes. CONCLUSIONS: The long-term prognoses of patients for whom dissection was omitted owing to negative sentinel lymph node metastases were similar to those reported previously-low recurrence and mortality rates. The frequency of axillary lymph node recurrence and the post-recurrence outcome differed between luminal and TN cases, with recurrence being more frequent in patients with the TN subtype. TN patients also had poorer prognoses, even after receiving additional dissection and anticancer agents after recurrence.

Expression of cyclooxygenase-2 in malignant and benign breast tumors.

Cyclooxygenase-2 (COX-2) is reported to play an important role in carcinogenesis. We examined COX-2 expression in patients with breast cancer and benign breast tumors. Immunohistochemical staining revealed a high level of COX-2 expression in malignant lesions of invasive ductal carcinoma (IDC) at a rate of 40% and a low level of expression in 15% of adjacent normal-appearing breast epithelia. Similarly, in ductal carcinoma in situ (DCIS), a high level of COX-2 expression was found in 80% of malignant lesions and a low level of expression in 50% of normal epithelia. Reverse transcriptional polymerase chain reaction (RT-PCR) performed in 7 of these cases disclosed that COX-2 expression was restricted to the malignant lesion. Further, all 10 cases of fibroadenoma and 10 cases of intraductal papilloma, both of which are benign tumors, had a high level of COX-2 expression. When overexpression of COX-2 was analyzed in relation to the clinicopathological features of the patients, no characteristic correlation was noted. Our results demonstrated that COX-2 is expressed in mammary tissue during tumorigenesis of the breast gland, suggesting that the cyclooxygenase isoenzyme may be a target for the prevention and treatment of breast cancer.

A case of diabetic mastopathy with multiple lesions mimicking breast cancer.

We report a case of diabetic mastopathy with multiple unilateral lesions in an insulin dependent patient. The patient was a 62-year-old woman with two hard tumors in the right breast, who had been treated with insulin for diabetes mellitus. Mammography revealed a highly dense tumor in the right breast, while ultrasonography showed two irregular hypoechoic lesions with marked posterior acoustical shadowing, suggesting scirrhous carcinoma. On magnetic resonance imaging the two lesions had slightly heterogeneous enhancement. Aspiration breast cytology showed insufficient cellular material for evaluation. Excisional biopsy was performed because the patient wanted confirmation and treatment. Fibrosis with dense lymphocytic infiltration around the lobules and ducts was diagnosed histopathologically. These findings were compatible with diabetic fibrous mastopathy. Although this disease is thought to be a diabetes-induced reaction of autoimmune origin, multiple lesions are rare. This is the first case of unilateral multiple lesions of diabetic mastopathy.

Monotherapy with paclitaxel as third-line chemotherapy against anthracycline-pretreated and docetaxel-refractory metastatic breast cancer.

We describe a patient with anthracycline-pretreated and docetaxel-refractory metastatic breast cancer who achieved a complete response after third-line chemotherapy with paclitaxel. A 59-year-old woman underwent modified radical mastectomy for advanced cancer in her left breast after local arterial neoadjuvant chemotherapy with anthracycline. Postoperatively anthracycline-containing adjuvant therapy was administered. Pulmonary metastases occurred 15 months after surgery, which did not respond to 4 cycles of second-line chemotherapy with docetaxel, given at 60 mg/m(2) every 3 weeks. Therefore 210 mg/m(2) of paclitaxel was given every 3 weeks as third-line monotherapy and induced a complete response with grade 3 neutropenia and hair loss as the major adverse effects. We suggest that paclitaxel is potentially effective as third-line monotherapy for anthracycline-resistant and docetaxel-refractory metastatic breast cancer.

Validation study of the UICC TNM classification of malignant tumors, seventh edition, in breast cancer.

BACKGROUND: The TNM classification of the Unio Internationalis Contra Cancrum was revised for the seventh edition. The major change concerning breast cancer is a change in the stages for patients with T0 or T1N1miM0. In the present study, the seventh edition of the TNM classification was validated in breast cancer. METHODS: The stages of 416 breast cancer patients, treated at our hospital in 1996, were classified according to the TNM classification, sixth and seventh editions, and their prognoses were compared. RESULTS: Case distribution using the sixth edition was stage 0, 56 cases (13.5 %); stage I, 158 cases (38.0 %); stage II, 130 [A, 102; B, 28] cases (31.2 [A, 24.5; B, 6.7] %); and stage III, 72 [A, 31; B, 8; C, 33] cases (17.3 [A, 7.5; B, 1.9; C, 7.9] %). According to the seventh edition, the stages for 20 patients, accounting for 19.6 % of IIA cases according to the sixth edition, decreased from IIA to IB. The 10-year overall survivals were stage 0, 91.1 %; stage I, 88.6 %; stage II, 80.8 %; and stage III, 63.9 % according to the sixth edition; and stage 0, 91.1 %; stage I, 88.8 %; stage II, 79.1 %; and stage III, 63.9 % according to the seventh edition. Although no significant differences were seen among the survival rates for stages 0 to II according to the sixth edition, there was a significant difference between stage I and II according to the seventh edition (p = 0.026). CONCLUSION: The latest revision of the TNM classification is appropriate for breast cancer from the perspective of prognosis.

Sentinel node tumour burden quantified based on cytokeratin 19 mRNA copy number predicts non-sentinel node metastases in breast cancer: molecular whole-node analysis of all removed nodes.

OBJECTIVE: The one-step nucleic acid amplification (OSNA) assay can assess an entire lymph node and detect clinically relevant metastases quantified based on cytokeratin 19 (CK19) mRNA copy number. The OSNA assay of all sentinel lymph nodes (SNs) and non-sentinel nodes (non-SNs) allows for the accurate measurement of tumour burden in either situation. We aim to reveal the usefulness of the OSNA assay regarding the prediction of non-SN metastasis. METHODS: The subjects consisted of 185 breast cancer patients who underwent axillary dissection after a metastatic SN biopsy and whose SNs and non-SNs were examined using the OSNA whole-node assay between 2009 and 2011. The non-SN tumour burden was classified as macrometastasis (CK19 mRNA ≥ 5000 copies/µl) or micrometastasis (250-5000 copies/µl). The relationship between SN and non-SN tumour burdens and predictors of non-SN metastasis were investigated. RESULTS: Among these 185 patients, 38 patients (20.5%) had macrometastasis and 58 (31.4%) had micrometastasis only in the non-SNs. Non-SN macrometastasis rates increased in direct proportion to the SN copy number: approximately 5% in patients with SNs with 250-500 copies; 20%, 500-5000 copies and 30%, ≥ 5000 copies. However, non-SN micrometastasis rates were approximately 30% regardless of the SN copy number. In multivariate analyses, the mean SN copy number, number of macrometastatic SN and lymphovascular invasion were significant for identifying non-SN macrometastases. CONCLUSIONS: The SN tumour burden quantified using the OSNA assay predicts non-SN metastases. A novel mathematical model to predict the non-SN tumour burden can be generated using the results of the OSNA assay.

Influence of lymphatic invasion on locoregional recurrence following mastectomy: indication for postmastectomy radiotherapy for breast cancer patients with one to three positive nodes.

PURPOSE: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. METHODS AND MATERIALS: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status. RESULTS: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). CONCLUSION: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.