The detection of non-palpating breast cancer might improve the survival of patients with whole breast cancer because it can be diagnosed at an early stage. Therefore, to standardize the quality of patient care, a published assessment guideline is necessary in a clinical setting. For this purpose, Japan and USA have independent guidelines with different approaches. “The evidence-based guideline for clinical treatment of breast cancer” that was published in June 2005 by the Japanese breast cancer society, is the first set of integrated guidelines pertaining to breast cancer in Japan. These guidelines are presented in the research questions (RQ) format. This paper explains 7 RQs (out of 31 RQs) and also discusses the recommendations pertaining to the diagnosis of nonpalpable breast cancer. The National Comprehensive Cancer Network (NCCN; USA) guidelines, which are widely recognized as one of the most reliable guidelines based on published evidences, also contain the diagnostic assessment of asymptomatic patients with a negative physical examination. This paper discusses pros and cons of each of the abovementioned guidelines as well as their clinical application. It is necessary to use both the Japanese and NCCN guidelines while understanding the differences between the two.

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In Japan, mammography was endorsed for breast cancer screening in women aged 40 and over by the Ministry of Health, Labor and Welfare in 2004. The spread of mammographic screening has caused an increase in the incidence of non-palpable breast cancer.
Precision reading for mammography is necessary to detect non-palpable breast cancer. When mass and focal asymmetric density is noted, it is important to analyze the density, density gradient, internal structure, margin and associated findings. Calcifications are classified by morphology and distribution mainly. It is necessary to distinguish secretor-type calcifications from necrotic-type calcifications.
The Iwate Cancer Association performed a population-based screening program for breast cancer using mammography combined with clinical breast examination of 42,065 women in Iwate Prefecture from 1999 to 2003. A total of 2,329 (5.7%) women were recalled and the 112 cases (0.27%) of cancer were detected in 114 breasts. Of 114 breast cancers, 40 (35%) were non-palpable and 74 (65%) were palpable. The early breast cancer (stage 0 and I) rate of the non-palpable group was significantly higher than that of the palpable group (90% and 47%, p = 0.0003). The node-negative rate of the non-palpable group was significantly higher than that of the palpable group (92% and 68%, p = 0.011).
It is expected that mammographic screening will be expanded and that the mortality rate from breast cancer in Japan will decrease, as in Europe and the United States.

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Background: Ultrasound (US) is a standard modality to diagnose breast diseases. To elucidate the usefulness of US in the diagnosis of nonpalpable breast cancers, we reviewed the cases that were treated at our institution.
Methods: Of the 106 cancers that were operated upon at the Tsukuba University Hospital between February 2004 and March 2005, 12 cancers were nonpalpable. We reviewed their US findings, results of US-guided fine needle aspiration cytology (FNAC), core biopsy results, and histological diagnoses.
Results: On US, 9 tumors appeared as masses. The US observations were valuable, but a confirmatory diagnosis could not be made. US-guided FNAC was performed in 8 cases; malignancy was suspected in 6 cases. US-guided core biopsy was performed in 9 cases, and it was diagnostic in 7 cases.
Conclusions: Nonpalpable breast cancers can be effectively detected by US, and the diagnosis can be confirmed by US-guided FNAC or core biopsy.

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Recently, the incidence of non-palpable or noninvasive breast cancer has increased. Consequently, criteria for choosing procedures to obtain pathological materials had changed. Fine needle aspiration biopsy cytology (FNA) and core needle biopsy (CNB) are both reliable procedures for detecting breast cancer. However, for non-palpable lesions, the diagnostic accuracy of CNB is higher. The main limits of FNA are the high rate of insufficient sampling and inability to determine invasiveness. CNB is an established alternative to surgical biopsy, and CNB can avoid excess surgical biopsies in a large number of patients.
In addition to accurate histological diagnosis, there is interest in obtaining prognostic information from CNB, especially for patients being considered for preoperative (neoadjuvant) therapy. CNB provides useful information about histologic type and grade. However, an unavoidable problem of CNB is underestimation of invasion. On the other hand, there is good concordance in particular for estrogen receptor (ER) and progesterone receptor (PR) between CNB and surgical excision.
Several aspects of CNB remains controversial, such as diagnosing papillary lesions by CNB, problems regarding tumor cell displacement after CNB, and management of lobular neoplasia (LN) on CNB.

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The development of new chemotherapeutic agents and regimens has contributed to reduced risk of cancer recurrence and prolonged patient survival. However, mild cognitive impairment (MCI), also known as “chemofog” or “chemobrain” following adjuvant chemotherapy for breast cancer has been reported since the late 1980s. Unfortunately, little is known about it's mechanism, type, severity, and episode length. This article reviewed related studies on the subject, and found that chemotherapy-induced MCI appears to occur in 10-40% of patients, and memory loss and lack of concentration are the most frequent symptoms. The symptoms are apparently transient, but take at least several years to disappear. Reviewed studies show a lack of clear understanding of what causes MCI directly. There is also a lack of consistency in symptom measurement. We point to the need to conduct well-designed studies which begin with a proper hypothesis. Future research needs to be randomized and longitudinal with a base measurement point before the chemotherapy cycle starts. Future studies must adopt an effective and sensitive method to measure MCI. The latest imaging technique, positron emission tomography (PET) may be a powerful tool. Also, all confounding factors, such as age, education, intelligence quotient (IQ), fatigue and depression, hormonal therapy and other treatments should be controlled within the study design. It is hoped that the results of such future studies will allow medical professionals to contemplate effective prevention, treatment and rehabilitation for MCI.

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Purpose: Seroma is the most common complication of mastectomy. The aim of this systematic review is to clarify the pathophysiology of seroma.
Materials and Methods: A computer-assisted MEDLINE search was conducted, and additional references were found in the bibliographies of these articles. The reference terms “breast cancer”, “mastectomy”, “seroma”, “lymphocele” and “lymphocyst” were used as both keyword and subject terms. The search was limited to studies published in English.
Results: The definition of seroma was highly variable across studies, but was most commonly a seroma large enough to be noticed by the patient or medical staff and affecting the patient's satisfaction in the immediate or acute postoperative period. So far, only limited data are available on the severity of seroma. With respect to the pathophysiology of seroma, the data indicated that several anatomical factors, especially dead space, likely contribute to seroma formation. However, it was obscure whether seroma was due to lymph-like fluid or exudate.
Conclusion: There is considerable variability in the way seroma is defined across studies, and its pathophysiology remains uncertain.

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Clinical studies have shown a correlation of HER-2/neu amplification/over-expression and favorable response to neoadjuvant chemotherapy and anti-HER-2/neu antibody treatment. However, contradictory findings also have been reported. Some tumors may develop resistance to neoadjuvant chemotherapy after an initial period of sensitivity. Our study attempts to evaluate the effects of neoadjuvant chemotherapy on HER-2/neu status in locally advanced breast cancer.
Thirty-nine patients with locally advanced breast cancers established by core needle biopsy received neoadjuvant chemotherapy and were compared with 60 patients with breast cancers who did not receive neoadjuvant chemotherapy. IHC for HER-2/neu was performed on paraffin sections of the core biopsy before treatment and the excised specimen following chemotherapy and scored as Negative (0-1+), 2+ and 3+. The results of the study and the controls were compared and analyzed using Fisher's exact test.
HER-2/neu IHC scores decreased in 28.5% (15/39) of patients receiving neo-adjuvant chemotherapy compared to 11.7% (7/60) of patients in the control (p < 0.013). HER-2/neu IHC status changed from strongly positive to negative (3+ to 0) in five of 39 (12.5%) in the study group and in 2 of 60 (3.3%) in control group (p = 0.104).
For patients receiving neoadjuvant chemotherapy in whom the tumor becomes refractory to chemotherapy or recurs, repeat testing for HER-2/neu status may be necessary. Elimination of HER-2/neu positive tumor cells may account for the changes in the IHC scores and the development of resistance to neoadjuvant chemotherapy.

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Background: It has been reported that immediate autologous tissue breast reconstruction after nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) is esthetically superior to autologous tissue reconstruction after conventional mastectomy (CM). We evaluated reconstructed breasts to determine whether these methods contribute to breast appearance other than skin texture.
Methods: Between April 1992 and September 2001, forty-two patients underwent immediate breast reconstruction using autologous tissue. Mastectomy options were NSM, SSM and CM. Postoperative photographs were evaluated using a subscale (volume, contour, placement, and inframammary fold) on a 0-2 point scale. Sternal notch to nipple distances of the affected and normal sides were measured with photographs to estimate nipple-areola complex (NAC) position. No corrective procedure was performed in a later phase before evaluation.
Results: NSM was performed in 22, SSM in 6 and CM in 14 cases. On esthetic evaluation, the NSM and SSM groups received 4.96 and the CM group received 4.63. There were no significant differences. In the NSM and SSM group, the NAC position rose in cases with partial necrosis or fat lysis compared with the no complication group (p = 0,004).
Conclusions: Autologous tissue breast reconstruction after NSM or SSM is esthetically equal to autologous tissue reconstruction after CM with regard to parameters other than skin texture. Preserved or simultaneously reconstructed NAC sometimes emphasizes nipple-areola asymmetry when breast deformity has occurred.

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Background: Although controversy exists, invasive lobular carcinoma (ILC) differs in its high frequency of microscopically positive margins after conservative therapy compared to invasive ductal carcinoma (IDC). If ILC could be recognized by imaging modalities, it would provide important information for surgeons. We tried to confirm whether it is possible to distinguish ILC from other invasive carcinomas by ultrasonography (US).
Methods: A total of 81 histologically confirmed cases of IDC, including 26 cases of papillotubular carcinoma, 28 cases of solid-tubular carcinoma and 27 cases of scirrhous carcinoma, as well as 24 cases of ILC were selected and retrospectively studied with regard to the features of mass lesions on US examination.
Results: The sensitivities of US for papillotubular carcinoma, solid-tubular carcinoma, scirrhous carcinoma and ILC were 88.5%, 100%, 92.6% and 91.7% respectively. We could divide invasive breast cancer into two groups by US findings. One group had a low frequency of malignant findings and consisted of papillotubular and solid-tubular carcinomas, and the other group had a high frequency of malignant findings and consisted of scirrhous carcinomas and ILC. However, there were no statistical differences between papillotubular carcinoma and solid-tubular carcinoma or between scirrhous carcinoma and ILC with regard to the US findings.
Conclusions: Scirrhous carcinoma, the most common type of IDC, and ILC are difficult to distinguish by US. Therefore it is difficult to separate ILC from IDC by US.

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Background: Assessment of pectoralis muscle invasion is important for treatment planning for breast cancer. We evaluated the usefulness of breast magnetic resonance (MR) imaging for the detection of tumor invasion of the pectoralis muscle in breast cancer patients.
Materials and Method: A total of 306 breast MR examinations were performed preoperatively. Three-dimensional gradient echo sequences, at a section thickness of 1.5 or 2 mm were obtained with administration of gadolinium-DTPA. All patients underwent surgery.
Results: In 33 breasts, disruption of the fat plane between tumor and muscle was noted. Seven of 33 cases showed muscle enhancement contiguous to enhanced tumors. Pathology reports indicated that 5 of 7 of the tumors involved muscle invasion. Of the 2 false positive cases, one showed muscle enhancement because of a previous biopsy, and the other was incorrectly interpreted as showing muscle enhancement. Of the 26 breasts which did not demonstrate muscle enhancement, none were found at surgery to have tumor involvement.
Conclusion: Enhancement of the pectoralis muscle correlates well with muscle invasion, but there are a few potential pitfalls. Disruption of the fat plane between tumor and muscle, without muscle enhancement, might not indicate tumor involvement of the pectoralis muscle.

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Real-time magnetic resonance (MR) imaging enables the application of percutaneous microwave coagulation for high-risk patients with metastatic liver tumours. The tumours, local vessels and bile ducts can be observed clearly in three-dimensional sections and a sufficient surgical margin can be confirmed on the MR image even during the coagulation procedure. MR-guided percutaneous microwave coagulation therapy is effective for treatment of not only primary liver tumours but also metastatic breast cancers in the liver, which are not diffuse but discrete, and difficult to treat with only chemo- and endocrine therapy. We report a 44-year-old Japanese woman who underwent modified radical mastectomy for right breast cancer (T1c N0 M0 Stage I). Three years after the operation, she developed two metastatic liver tumours and was treated by MR-guided percutaneous microwave coagulation, achieving a complete response (CR) without any recurrence for 15 months as of the present. The most beneficial aspect of MR-guided percutaneous microwave coagulation is its safety. It is only minimally invasive and can be repeated. This therapy, therefore promises to prolong the disease free period. Additional clinical trials will be valuable to delineate the effectiveness and safety of MR-guided percutaneous microwave coagulation therapy for controlling the liver metastases of breast cancer.

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We report a case of phyllodes tumor (PT) with multiple lesions partly mimicking fibroadenoma (FA). A 43-year-old woman was referred to our institute because of a left breast mass which was diagnosed as FA clinically. During the follow-up, the mass gradually enlarged and excisional biopsy was performed to rule out malignant lesion. On histological examination, the tumor consisted of three different components; a lesion diagnosed as FA, another lesion as benign PT, and the other lesion as borderline PT. Finally, the tumor was diagnosed as borderline PT. Stromal cellularity may vary from area to area in any given PT. If there are some disagreements among the findings of imagings and cytology for the diagnosis of FA, as was seen in our case, the possibility of coexistence of PT should be considered.

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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.

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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 × 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 × 2.5 × 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 × 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.

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A surgically resected case of giant mucinous carcinoma of the breast that had remained untreated for 2 years is reported. A 64-year-old postmenopausal woman presented with a large right breast mass (17.4 × 16.5 × 14.5 cm). Although she had noticed a mass in the right breast 2 years previously, she had not sought treatment. Mucinous carcinoma was diagnosed by core needle biopsy and she underwent right modified radical mastectomy with a free skin graft. There were no lymph node metastases or distant metastases. Fourteen months postoperatively, she remains well without evidence of tumor recurrence. Although several reports have suggested that pure mucinous carcinoma of the breast has a favorable prognosis, we need to follow this case until the clinical behavior and the outcome become clear.

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We encountered a case of occult contralateral breast cancer, previously undetected by conventional imaging such as mammography (MMG) and ultrasonography (US), but incidentally detected by contrastenhanced magnetic resonance imaging (CE-MRI). We present it here with a review of the literature. A 67-year-old Japanese woman was referred to our hospital in October 2000 because of a 1.5 cm right breast lump detected in a medical checkup. MMG, US and fine needle aspiration cytology revealed a cancerous lesion during the right breast. No mass lesion was palpable nor was any detected by MMG or US in the left breast. Bilateral breast CE-MRI was performed for more detailed evaluation. Consequently, an occult contralateral breast cancerous lesion was detected incidentally by CE-MRI, with the images showing rapid initial enhancement of time to signal intensity curves. Before surgery, bilateral breast lesions were diagnosed as invasive ductal carcinoma by open biopsy. She underwent bilateral breast conserving surgery with bilateral axillary lymph node dissection. The postoperative course was uneventful and no recurrence has been noted as of January 18th, 2004. CE-MRI of the contralateral breast should be of value as a routine screen in those patients with a known or suspected malignancy in one breast considering the limits of breast cancer detection by such conventional modalities as MMG and US.

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