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1. For operable, postmenopausal, hormone receptorpositive, HER2-negative breast cancer, preoperative endocrine therapy may be considered for the purpose of breast conservation (Grade C1). 2. Preoperative endocrine therapy improves the breast conservation rate in premenopausal breast cancer as well as postmenopausal breast cancer. However, it is not generally recommended since evidence is scarce (Grade C2).

We assembled needed data on the prevalence and characteristics of BRCA1/2 in Japan.Our study of BRCA1/2 collected data at eight institutions in Japan on 320 individuals with a strong family history of breast cancer, according to the NCCN guidelines, by the end of March 2012.Among 260 proband cases, 46 (17.7 %) were positive for BRCA1, and 35 (13.5 %) were BRCA2-positive. Therefore, the total pathological mutation rate was 30.7 %. Pathology data after breast surgery were obtained from 37 cases of BRCA1 mutation, 23 (62.2 %) of which were triple negative (TN). On the other hand, 29 cases (82.9 %) of BRCA2 mutations were Luminal type. The most prevalent BRCA1 mutation site was L63X, found in 10 families. L63X was reported previously by studies in Japan, and it may be a founder mutation. We found two cases of large deletion detected by multiplex ligation-dependent probe amplification. One was an entire deletion of exon 20 and the lacked exons 1-9. TN with a family history of ovarian cancer was 11/20 (55 %). TN under 40-year-old (y.o.) 15/23 (65.2 %) and TN with one or more breast cancers in family history 17/32 (53.1 %) showed higher incidences of BRCA1 mutation.Hereditary breast and ovarian cancer (HBOC) may have nearly the same prevalence in Japan as in the US or Europe. If TN cases are taken into account, the ratio of BRCA1 is higher. L63X may be one of the founder mutations in Japan. A nationwide database of HBOC is important to develop risk models for BRCA1/2 carriers in Japan.

We evaluated the expression of aldehyde dehydrogenase 1 (ALDH1) between primary breast lesions and pulmonary metastatic (PM) lesions in breast cancer patients. We retrospectively analyzed the clinicopathological features and the expression statuses of ER, PR, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions and evaluated the discordance rates in the expressions of these markers between the primary and metastatic lesions, and also the prognostic value of these factors. None of the PM patients had metastases at any other sites, and all had undergone curative breast cancer surgery. The pulmonary operation was partial resection in 15 (88 %) patients and lobectomy in 2 (12 %) patients. The median overall survival (OS) after resection of the PNs (OS) was 48 months. The discordance rates in the expressions of ER, PR, HER2, Ki67 and ALDH-1 between the primary and metastatic lesions were 0, 29, 21, 43 and 50 %, respectively. There was significant discordance in the biomarkers between the primary tumors and the metastatic lesions.

Sensory loss or paresthesia due to division of the intercostobrachial nerve (ICBN) is a complication of axillary lymph node dissection (ALND). Preservation of the ICBN may be of value, but few prospective studies have shown an impact of preservation on sensory changes or health-related quality of life (HRQOL) after breast cancer surgery. This prospective study was performed to evaluate the association between ICBN preservation and sensory change and HRQOL at 1 (baseline), 6, 12, and 24 months after breast cancer surgery in 140 patients. The sensory examination included dysesthesia, paresthesia, and abnormal touch and pain sensation in the upper arm. Division of the ICBN did not influence the frequency or severity of subjective dysesthesia and paresthesia. There was no marked difference in touch or pain sensation at baseline between patients with a preserved (group P) and divided (group D) ICBN. In group P, the percentage of patients aware of a sensory deficit or loss decreased with time, and that of patients aware of a hypersensitive sensation increased. These changes did not occur in group D, leading to a significant difference between the groups at 24 months. The main difference between the groups was the area with reduced touch or pain sensation. This area decreased with time in group P, but not in group D. ICBN preservation or division did not influence HRQOL. ICBN preservation in ALND has a benefit of a reduced area with long-term axillary hypoesthesia, but has no influence on improvement of pain and HRQOL.

To define the factors associated with increased risk of isolated locoregional failure that may justify postmastectomy radiotherapy in patients with T1/2 breast cancer and 1–3 positive lymph nodes. Between 1990 and 2002, 248 patients who had pT1–2 breast cancer and 1–3 positive lymph nodes were treated with mastectomy without radiotherapy (age 32–84, median 54). Median follow-up time was 82 months (range 2–189 months). For all patients, the 8-year isolated locoregional failure-free rate was 95 %. In univariate analysis, hormone receptor status and administration of hormone therapy were statistically significant factors, and vascular invasion was the borderline significant factor for isolated locoregional failure-free rates (P = 0.0377, 0.0181, and 0.0555, respectively). The 8-year isolated locoregional failure-free rates were 98 % for patients with positive hormone receptor status and 90 % for patients with negative hormone receptor status, 97 % for patients who received hormone therapy and 89 % for patients who did not receive hormone therapy, 92 % for patients with vascular invasion and 97 % for patients without vascular invasion. In multivariate analysis for hormone receptor status and vascular invasion, the former was statistically significant (P = 0.0491) and the latter was borderline significant (P = 0.0664). When patients had both negative hormone receptor and positive vascular invasion status, the 8-year isolated locoregional failure-free rates decreased to 83 %. With regard to patients who had pT1/2 breast cancer and 1–3 positive lymph nodes, isolated locoregional failure was not common in general; however, patients who had both negative hormone receptor status and vascular invasion were comparatively high-risk patients for isolated locoregional failure.

The most common diagnostic procedure in the United States for mammographically detected nonpalpable lesions is a combination of a vacuum-assisted biopsy device and a prone-type biopsy table. We have used an upright-type stereotactic mammography unit without a digital imaging system instead of the prone table.Five-hundred ten biopsies of 506 mammographically detected nonpalpable breast lesions in 488 patients, consisting of 445 lesions with microcalcifications alone, 39 masses without calcifications, and 22 with both masses and microcalcifications, were attempted using a combination of a vacuum-assisted device (Mammotome) and an upright unit without a digital imaging system in a sitting position between May 1999 and February 2007.Breast tissue was obtained in 497 biopsies. Microcalcifications were confirmed radiographically in the tissue of 447 out of 459 biopsies from lesions with microcalcifications (97.4 %). One hundred thirty-seven were diagnosed as malignant, 10 as atypical ductal hyperplasia, 345 as benign, and 1 was not diagnosable. The underestimation rate was 28.0 %. Overall, 26 patients (5.1 %) had vasovagal reactions, while 19 (3.8 %) experienced mild subcutaneous bleeding. Two hundred fifty of 350 lesions, for which biopsy diagnoses were benign, were followed for a median period of 33 months. Four lesions turned out to be malignant. The false-negative rate was 2.8 %.The biopsy technique using the combination of the Mammotome and an upright unit without a digital imaging system is cost-effective, safe, and accurate, and should be regarded as one of the standard biopsy methods for mammographically detected nonpalpable lesions.

The impact of aggregate of risk factors on isolated locoregional failure after mastectomy without radiotherapy was assessed.We reviewed 1091 patients who had stage I-III unilateral breast cancer and received mastectomy between 1990 and 2002.Median follow-up time was 67 (1-175) months. On multivariate analysis, four or more positive axillary lymph nodes (AXLN ≥4), pT4, primary tumor larger than 5 cm (T5 cm), severe lymphatic invasion (ly2-3), and negative hormone receptor status (HR negative) were the statistically significant risk factors (hazard ratios 5.78, 2.31, 2.47, 2.99, and 3.40, respectively). The 8-year isolated locoregional failure-free rates of patients with single risk factor were 88% for AXLN ≥4, 93% for pT4, 93% for T5 cm, 98% for ly2-3, and 97% for HR negative. Considering impact on isolated locoregional failure, AXLN ≥4 was termed the major risk factor and other factors were termed minor risk factors. The 8-year isolated locoregional failure-free rates were 98% for patients with only 0-1 minor risk factors (low-risk group), 86% for patients with the major risk factor alone or with only 2-4 minor risk factors (intermediate-risk group), 72% for patients with the major risk factor plus 1-2 minor risk factors (high-risk group), and 28% for patients with the major risk factor plus 3-4 minor risk factors (very high-risk group).Aggregate of risk factors increased the risk of isolated locoregional failure significantly. Patients with the major risk factor plus one or more minor risk factors seemed to be candidates for postmastectomy radiotherapy.

There is still controversy concerning the indication of postmastectomy radiotherapy (PMRT) for pT3N0M0 breast cancer. To identify the candidates for PMRT in this subset, we investigated failure patterns, and searched for risk factors for isolated locoregional failure in pT3N0M0 breast cancer after mastectomy without PMRT. Among 1,176 patients who received mastectomy without PMRT for untreated unilateral breast cancer between 1990 and 2002, 64 patients (5%) had pT3N0M0 breast cancer (age 30–81 years; median 52.5 years). Isolated locoregional failure as the initial failure occurred in three patients. For all 64 patients, the 8-year failure-free survival rate, the isolated locoregional failure-free rate, and the distant failure-free rate were 76, 93, and 82%, respectively. Incidence of isolated locoregional failure as the initial failure was 18% (2/11) for patients 40 years or younger and 2% (1/53) for patients older than 40 years. The 8-year isolated locoregional failure-free rates were 73% for patients 40 years or younger and 98% for patients older than 40 years (p = 0.0135). Concerning pT3N0M0 breast cancer, incidence of isolated locoregional failure was comparatively low after mastectomy without PMRT. Routine use of PMRT for all pT3N0M0 patients seemed to be unacceptable. PMRT may be useful for younger patients because of the comparatively high incidence of isolated locoregional failure. Because of the small number of cases in our series, further studies are necessary to determine the usefulness of PMRT for younger patients with pT3N0M0 breast cancer.

Breast cancer screening by mammography (MMG) has recently increased in Japan. Suspicious lesions are therefore being detected more and more by MMG and the number of benign biopsies is increasing. It is thus important to examine which pathologically benign lesions were read as suspicious on MMG to reduce the number of biopsies in the case of benign breast lesions. Of 299 category 3 or 4 lesions on MMG, 39 histologically benign lesions with calcification were reviewed and compared with the mammograms by a pathologist and a radiologist. The Japan Mammography Guidelines were used for MMG interpretation. In mastopathy lesions, small round segmental calcifications and pleomorphic clustered calcifications were assessed as suspicious. The suspicious type of calcification in fibroadenoma was small round clustered. The calcifications in fibroadenoma may be seen as small round when the fibroadenoma is rather young, and assessed as suspicious. Some types of calcifications in mastopathy and fibroadenoma were assessed as borderline by MMG. We should therefore collect data from more benign cases with suspicious calcifications on MMG and elucidate the diagnostic criteria in MMG findings of such calcifications.

We report two cases of occult breast cancer in which masses were completely nonpalpable and positron emission tomography-computed tomography (PET-CT) was extremely helpful in identifying the primary tumor. Case 1 involved a 56-year-old woman with enlarged lymph nodes 3 cm in size in the axilla. Based on excisional biopsy, axillary lymph node metastasis of breast cancer was suspected but an obvious primary tumor in the breast was not identifiable on mammography, contrast-enhanced CT, or ultrasonography. Faint accumulation of fluorodeoxyglucose (FDG) was noted only on PET-CT, so the site was considered to be the primary site, and operation was performed. As a result of postoperative pathological examination, ductal carcinoma in-situ (DCIS) was diagnosed. Case 2 involved a 55-year-old woman with enlarged lymph nodes 3 cm in size in the axilla. Based on the excisional biopsy, axillary lymph node metastasis of breast cancer was suspected. In this case as well, an obvious primary tumor was not identifiable with palpation or mammography. On PET-CT, faint accumulation of FDG was noted in the vicinity of the CD regions, or upper and lower outer quadrants. When contrast-enhanced CT and ultrasonography were performed, a faint nodular opacity less than 1 cm in size corresponding to this site was found and diagnosed as the primary site, operation was subsequently performed. Pathologic diagnosis indicated invasive cancer. PET-CT is a helpful option for the diagnosis of occult breast cancer with primary sites that conventional imaging studies have difficulty identifying.

Most of the discordant cases between biochemical and immunohistochemical (IHC) assays for hormone receptor (HR) status in breast cancers are due to negative findings from the biochemical assay but positive IHC findings. However determining HR status based on IHC only in biochemically HR negative breast cancers has never been studied. The aim of this study is to examine the histological characteristics in immunohistochemically HR positive but biochemically HR negative breast cancers.IHC staining for HRs in 345 biochemically HR-negative breast cancers was done. The relationship between HR status by IHC and the histological characteristics was assessed.In 345 cancers, 105 (30.4%) were estrogen receptor- (ER) or progesterone receptor- (PR) positive by IHC. The enzyme-immunoassay (EIA) HR titer was higher in immunohistochemically HR-positive tumors (ER: 2.7 fmol/mg protein; PR: 0.8 fmol/mg protein) than in negative tumors (0.6 fmol/mg protein in both HRs). IHC-assessed ER positivity on histological sections was high in some tumor types, such as mucinous carcinoma (77.8%), invasive micropapillary carcinoma (66.7%), and infiltrating ductal carcinoma of no special type with abundant stroma (60.2%). Among infiltrating ductal carcinomas of no special type, low nuclear grade tumors were all ER positive and high nuclear grade tumors showed low ER positivity by IHC, even in biochemically HR negative cancers.The IHC-assessed HR status may reflect tumor cell behavior, such as overall and disease-free survival and endocrine response, better than HR status as assessed by the enzyme-immunoassay method. Immunohistochemically HR-positive but biochemically HR-negative breast cancers include infiltrating ductal carcinomas of no special type with low nuclear grade and some tumor types with high stromal content. We can assess the true HR status by IHC especially these tumors.

More effective methods of preventing and treating breast cancer are being sought by clinicians every day, and new drugs and interventions for overcoming this cancer are being energetically evaluated. At present, there are wide treatment options and many different objectives for breast cancer. These circumstances led us to seek information about the relative costs of the different medical options for the prevention and treatment of breast cancer and to try to ascertain whether one course of action is more efficient than other courses. Economic evaluation of healthcare is indispensable for selection of the best alternatives among medical interventions which are becoming more diverse day after day. The total medical expenditure continues to rise each year and some sort of evaluation from an objective and external viewpoint is required to provide the information with which to suppress this rise. This paper surveys the three major reports published on this topic to date, for the purpose of demonstrating the importance and necessity of performing an economic analysis of the treatment and prevention of breast cancer. The three reports to be surveyed pertain to: (1) cost-effectiveness analysis of adjuvant chemotherapy for patients with lymph node negative breast cancer, (2) cost utility analysis of first-line hormonal therapy in advanced breast cancer, namely comparison of two aromatase inhibitors to tamoxifen, and (3) cost-effectiveness analysis of tamoxifen in the prevention of breast cancer. In addition, this paper discusses the advantages, limitations and perspective for the future of the economic evaluation of healthcare for breast cancer. (1) The authors concluded that if the average risk of all women of undergoing recurrence after this therapy is assumed to be 4% per year, adjuvant chemotherapy is definitely of benefit for node-negative, estrogen receptor-negative breast cancer patients. They additionally stated that this benefit decreases markedly if the changes in long-term survival are less than those in disease-free survival. In this connection, they pointed out that the benefit is considerably smaller among postmenopausal 60-year-old women. (2) The incremental cost per quality-adjusted progression-free life year (QAPFY) for letrozole and anastrozole, relative to tamoxifen, was Can $12, 500-19, 600, which was lower than the criterion level (US $50, 000). On the basis of this result, the authors concluded that these two drugs are economically acceptable. Furthermore, when efficacy and cost effectiveness were analyzed together, it was concluded that letrozole is in fact preferable to anastrozole. (3) The model analysis of tamoxifen’s cost effectiveness among women at increased risk for breast cancer yielded the following results. In the base-case analysis, involving the calculation of the costs and benefits of 5-year tamoxifen administration, the incremental cost effectiveness of tamoxifen was $41, 372 per life-year gained for women age 35 to 49 years, whereas for women age 50 to 59 years and 60 to 69 years, these values were $68, 349 and $74, 981, respectively. For women who had undergone hysterectomy and thus had no risk of the onset of endometrial cancer, the incremental cost effectiveness of tamoxifen was $46, 060 per life-year gained. Medico-economic evaluation of breast cancer is very significant and valuable and is expected to stimulate efficient utilization of healthcare resources. It can provide important information to physicians, patients, insurers, pharmaceutical and other industries, healthcare policy planners, and others.

The next step for breast cancer specialists, who have created and published the Breast Cancer Treatment Guidelines to evaluate of health care quality and who are ahead of many other clinicians in this respect, is to articulate the ideal form of evaluation that adequately combines evaluations from various perspectives.

Since standard radical mastectomy was established by Halsted for breast cancer, surgical procedures for breast cancer have been changed according to the results of randomized controlled trials. Breast-conserving treatment is now regarded as a standard local treatment for early breast cancer. More recently, sentinel node biopsy is becoming popular as an alternative procedure to axillary node dissection for nodal staging. These new procedures have been believed to be better in terms of patients' quality of life in comparison with previous surgical procedures without impairing prognosis. Many studies regarding the quality of life (QOL) of patients after such procedures have been reported. Here we review those data, especially of studies comparing quality of life of patients after mastectomy and breast-conserving treatment, and of those after axillary node dissection and sentinel node biopsy. Viewpoints and issues on surgical treatment-related QOL are discussed.

An 80-year-old woman visited our hospital with a massive ulcerated tumor in the upper lateral quadrant of the right breast. Her performance status was 2. Histopathologically, a mass consisting of a huge primary tumor and metastatic axillary lymph nodes was seen and invasive ductal carcinoma was diagnosed. Both estrogen and progesterone receptors were negative. Herceptest (DakoCytomation, Glostrup, Denmark) showed 2 + staining and HER2 amplification was detected by fluorescent in situ hybridization. CT revealed multiple lung metastases. Her old age and performance status of 2 made aggressive chemotherapy difficult. After receiving 5'-DFUR 600 mg/day as the first line treatment for two months, the tumors progressed. As second-line treatment, single agent therapy with a loading dose, a trastuzumab 4 mg/kg followed by 2 mg/kg weekly was recommended. The patient also received 60 Gy radiotherapy. Six months after the second line treatment, the breast tumor disappeared and only a scar remained on the chest wall and axilla. CT showed no lung tumors. During the trastuzumab treatment, no adverse effect was observed. Her performance status improved to zero, and she is alive and free from the disease 24 months after the disappearance of the tumor.

Seroma, a collection of serous fluid, is the most common problem after breast surgery. The aim of this study was to review the effect of mechanical closure of dead space on seroma formation after breast surgery. There are two mechanical methods for closure of the dead space beneath skin flaps: compression by external pressure, and fixation of the flaps with sutures. There is no evidence to suggest that the routine use of a pressure garment or compression dressing is beneficial. However, it appears that suture flap fixation does reduce seroma formation, simplify postoperative care and dressing, and thus allow early removal of drains and discharge. Drains are helpful for mechanical closure of dead space, but in breast-conserving surgery this technique may preclude the use of a drain. However, previous studies have often been small in scale and poor in quality. Further studies should examine the effect of this technique on quality of life, cosmesis, and medical economics.

We present a patient with pulmonary metastasis from breast cancer who received S-1 (TS-1) and maintained complete response for approximately 10 years after recurrence. A 51-year-old woman underwent modified radical mastectomy for left breast cancer in November 1991. Her cancer was postoperatively classified as pT2 pN0 M0 Stage IIA. As postoperative adjunctive treatment, tamoxifen and hexylcarbamoyl 1-5-FU (HCFU) were given. During the administration period (30 months after surgery), a solitary pulmonary metastasis occurred. Three months after the start of S-1 (100 mg/body/day), the tumor disappeared on images. Thereafter she took S-1 orally for approximately 10 years, and the pulmonary metastatic focus maintained complete response. In addition, no recurrent focus was observed. The adverse events observed during S-1 treatment were nausea, low-grade neutropenia and pigmentation of fingers. All were mild, and S-1 could be continued. Our case illustrates two important characteristics of S-1. First, S-1 was effective even though this patient had a lung metastasis during adjuvant treatment with HCFU. S-1 is a combined formulation containing 5-chloro-2, 4-dihydroxypyrimidine (CDHP; gimestat), which inhibits an enzyme that metabolites 5-FU, dihydropyrimidine dehydrogenase (DPD). Therefore, high 5-FU concentrations are maintained with S-1, and S-1 may be effective in the patients who do not respond to other fluoropyrimidine agents. Second, since S-1 toxicity was mild, long-term treatment for approximately 10 years was possible. Since S-1 contains potassium oxonate (OXO; otastat), gastrointestinal toxicities, the main adverse events of 5-FU agents, could be reduced. The purpose of treatments for metastatic breast cancer is to maintain favorable quality of life (QOL), as well as to improve survival. S-1 could be a valuable agent for breast cancer treatments, since it showed clinical efficacy and mild toxicity, and can be given orally.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign breast disease that presents as a localized breast mass. Breast tissue affected by PASH is characterized by a dense, collagenous proliferation of mammary stroma, forming interanastomosing capillary-like spaces. The importance of this benign lesion lies in distinguishing it from low grade angiosarcoma. We report a case of a 38-year-old woman who presented with a rapidly growing breast tumor. She visited our hospital with a complaint of a painless right breast mass. Physical examination revealed a 3.6 x 2.2 cm, oval, elastic-firm, well-defined and easily movable mass. Mammograms revealed no discrete mass or calcifications. Sonographic examination revealed a 3.5 x 2.5 x 2.2 cm, oval, well-defined and homogenous hypoechoic mass without a cyst. A fine-needle aspiration sample of the breast mass showed some clusters of epithelial cells with small papillary structures and many scattered stromal cells with naked nuclei. Based on these findings, a provisional diagnosis of fibroadenoma was made and the patient was followed up. One year after the first visit, the mass enlarged rapidly and a follow-up mammogram revealed an 8.2 x 5.5 cm circumscribed mass without calcifications. Given the history of rapid growth of the mass, tumor excision was performed. The excised tumor was well demarcated and had a smooth external surface. Histologic examination revealed normal breast ducts and lobules, and specific proliferative epithelial changes were not seen. The lobular and duct structure of the breast parenchyma were separated by an increased amount of stroma. The fibrous stroma contained numerous anastomosing slit-like spaces. Isolated spindle cells appeared intermittently at the margins of the spaces resembled endothelial cells. Immunohistochemical staining showed that endothelial cells lining true blood vessels were positive for Factor VIII-related antigen, but the spindle cells were negative for Factor VIII. Pseudoangiomatous stromal hyperplasia was diagnosed.

A rare case of intracystic papillary carcinoma (IPC) with invasion had synchronous metastases to the liver at presentation. A 57-year-old postmenopausal woman noticed a right breast tumor 7 months prior to admission. Mammography showed an oval mass measuring 3.1 cm in diameter with no calcification, and ultrasonography showed an intracystic tumor with a papillary growth pattern. Fine-needle aspiration cytology revealed adenocarcinoma. Excisional biopsy revealed intracystic solid papillary carcinoma with invasion. The tumor was a clear-cell type with extracellular mucin. Two months after the initial biopsy, a screening ultrasonographic examination of the liver showed multiple hyperechoic masses. Abdominal contrast-enhanced CT scan and magnetic resonance imaging (MRI) showed multiple hypervascular masses compatible with metastatic tumors. No suspicious lesions were detected on examinations for malignancy in other organs. Distant metastases in cases of IPC with invasion are very rare. The potential of distant metastasis in IPC with invasion and the difficulty of evaluating invasive foci should be recognized. Careful evaluation of distant metastases is recommended.

Two rare cases, each with a solitary brain metastasis from breast cancer with extensive nodal metastases as the first site of distant metastasis, were locally treated with surgery and irradiation. The outcome of the two treated cases indicated an excellent and non-recurrent post-therapeutic survival period of more than 3 and 8 years, respectively. In a 50-year-old woman (Case 1), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with doxorubicin and tegafur-uracil (UFT) and hormonal therapy with tamoxifen for left breast cancer. The brain metastasis was treated twice surgically followed by radiotherapy. One year and 6 months later, local recurrence of the brain metastasis appeared and was treated surgically again. No other treatment was done thereafter. Since then, no other distant or lymph node metastasis occurred, and to date her outcome has been non-eventful for 8 years and 5 months. In a 63-year-old woman (Case 2), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with cyclophosphamide, epirubicin and fluorouracil (CEF) for right breast cancer. The brain metastasis was treated locally with surgery and irradiation of 50 Gy. She thereafter received no further treatments. Since then neither distant metastases nor local recurrence have developed, and to date the post-treatment outcome has been uneventful for 37 months. Our findings suggest that patients who developed a solitary brain metastasis as the first site of distant metastasis from breast cancer have a chance of achieving long-term disease-free survival when treated with aggressive local therapy, even in the presence of extensive lymph node metastases at the primary surgery site for breast cancer.

Ipsilateral breast tumor recurrences (IBTR) after breast-conserving treatment include two different entities: true recurrence (TR) thought to occur when residual cancer cells grow gradually to detectable size and new primary (NP) thought to be de novo cancer independently arising in the preserved breast. The patients with ipsilateral breast tumor recurrence (IBTR) are potentially at high risk for subsequent distant metastasis, but many studies do not distinguish between these types of recurrence. The aim of this study is to clarify the biological difference between TR and NP, and to show the clinical significance of classifying IBTR into these two types of recurrence.A total of 172 patients with IBTR after breast-conserving therapy from the cohort of a long-term large scale study (Research of cancer treatment from the Ministry of Health, Labor and Welfare of Japan (no.13-9)) were analyzed. We classified IBTRs as TR or NP based on tumor location and pathological findings. The characteristics of the primary tumors of TR and NP were compared. Survival rates and risk factors of each type of IBTR were examined by the Kaplan-Meier method. The results of salvage surgery were also analyzed.Of the 172 patients, 135 patients were classified as TR and 26 as NP. Eleven cases could not be categorized. The primary tumor of TR was characterized by a high rate of lymph node metastasis (37.8%) and short disease-free interval (mean DFI; 46.6 months) while that of NP showed a rather low lymph node positivity (8.7%) and longer DFI (62.1 months). The risk factors for TR were young age, positive surgical margin, omission of irradiation and positive lymph node metastasis. Those for NP were young age, omission of irradiation and contralateral breast cancer after the primary operation. The 5-year survival rates after IBTR were 71.0% in TR and 94.7% in NP (p=0.022). Salvage operation was performed in 136 IBTRs. Eighty-one patients underwent salvage mastectomy and 55 patients underwent repeat lumpectomy. Five-year survival rates after salvage operation were 75.7% for mastectomy and 84.2% for lumpectomy (N.S.). Twenty percent of patients who underwent repeat lumpectomy developed secondary local relapse within 5 years after salvage treatment. The risk factors for secondary local relapse were analyzed. Limited to cases of IBTR which received radiation therapy after the primary operation, NP was the only factor influencing secondary local relapse by univariate analysis.TR and NP show clinically quite different features; time to occurrence, characteristics of the original tumor, prognosis and risk factor profile for IBTR were all different. Classifying IBTR as TR or NP can provide clinically significant data for the management of IBTR.

We report a very rare case of breast carcinoma which possibly arose from the duct of the nipple and formed a nipple mass. A 71-year-old woman presented with an elastically hard and enlarged right nipple, 3.5x 2.8 cm in size. Mammograms and ultrasonograms suggested a benign tumor of the nipple, but histological examination revealed invasive ductal carcinoma. No Paget's cells were found in the epidermis. Modified radical mastectomy was performed. Both estrogen and progesterone receptors were positive. One of the nine axillary nodes dissected had metastatic foci. To our knowledge, this case is only the second reported case of invasive ductal carcinoma originating from the nipple. Differential diagnosis and histogenesis are discussed.

Background The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR+) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757–62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported. Methods Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety. Results Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41–0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33–0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients. Conclusion Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR+/HER2− advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.