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The patient is an 85-year-old female who had previously undergone a mastectomy for right breast cancer at the age of 42 years. In September 2020, she visited our hospital with a chief complaint of a chest wall tumor. Physical examination revealed a 3×3 cm ulcerative lesion on the right side of the center chest wall. She underwent a skin biopsy of the tumor under local anesthesia and was diagnosed with a recurrence of right breast cancer(ER positive, PR positive, HER2 negative). PET-CT revealed localized skin thickening on the right side of the sternum and FDG accumulation in the same area, with no other findings suggestive of distant metastasis. Treatment was started with anastrozole and is still ongoing. In this article, we report a very rare case of recurrence 43 years after surgery.

An 83‒year‒old woman received trastuzumab plus anastrozole as first‒line chemotherapy for inflammatory breast cancer in her left breast. Following the treatment, the induration and redness in her breast gradually improved; however, 2 days after receiving the 5th course of chemotherapy, she developed dyspnea and was referred to the emergency room. Her SpO2 was 88%; her KL‒6 level had increased to 2,613 U/mL; and a chest CT scan showed ground‒glass opacity in the bilateral lung fields, yielding a diagnosis of interstitial pneumonia requiring steroid pulse therapy. The dyspnea improved immediately after steroid administration, and the patient was discharged 20 days after hospitalization. Thereafter, the steroid dosage was gradually lowered to 5 mg/day. We discontinued steroid therapy after a chest CT confirmed the reduction of ground‒glass opacity. However, she was later readmitted for interstitial pneumonia for which she was readministered steroid pulse therapy. Trastuzumab‒induced interstitial pneumonia is rare, but we must be aware of the possibility that patients may develop severe pulmonary disorders or experience cardiotoxic effects.

A 68-year-old woman had undergone mastectomy for right breast cancer when she was 60 years of age. The histopathological diagnosis had been scirrhous carcinoma, T1N0M0, stage Ⅰ. She had received anastrozole as the adjuvant therapy for 5 years. Eight years after the operation, she consulted our department because of a lump on the right chest wall. The metastatic work-up revealed no evidence of metastases. Tumorectomy was performed. Histopathological findings from the surgically resected specimens showed scirrhous carcinoma, positive for ER and PgR, and negative for HER2/neu protein expression. The Ki-67 positive cell index was 25%. Therefore, we diagnosed the patient with local recurrence of breast cancer. Since surgical margins were positive, irradiation was performed at the recurrence site, and letrozole was administered. Local recurrence is a target of the curative treatment and requires a multidisciplinary approach, including surgery, drugs, and radiation therapy. We report a case of local recurrence of breast cancer 8 years after mastectomy.

Purpose: There are many reports that describe the effectiveness of aromatase inhibitors as endocrine therapy after breast cancer surgery. However, there are few detailed evaluations of patient adherence to anastrozole(ANA)therapy. Here, we evaluated the adherence to ANA therapy in postoperative patients with primary breast cancer., Methods: We investigated 102 postoperative patients with primary breast cancer without distant metastasis, who received ANA at JCHO Kyusyu Hospital. We calculated the medication continuation rate and disease-free survival at 5 years from the initiation of medication. The reasons for medication discontinuation and alternative drug therapy after ANA therapy discontinuation were also investigated. Re- sults: The 5-year continuation rate of ANA treatment alone was 79%(81/102). The rate of all patients who continued ANA treatment, including 9 who changed to other drugs, was 88%(90/102). The most frequent ANA discontinuation reasons were progressive disease(8 cases), arthritis(5 cases), and nausea(3 cases). The disease-free survival rate was 92%(94/102), and the overall survival rate was 97%(99/102)., Conclusion: ANA showed a high continuation rate. Adherence of ANA in postoperative patients with breast cancer was well maintained, even when the treatment was changed to other drugs due to adverse events.

We report the case of a patient in which S-1 plus anastrozole was administered as first-line chemotherapy for Stage IV breast cancer with skin invasion, multiple lymph node metastasis, and lymphangitis carcinomatosis. A 77-year-old woman had a mass destroyed immediately outside the axilla with dry coughs. An 11mm unpalpable mass in the right breast and an axillary mass were confirmed to be scirrhous carcinoma(Luminal type B), respectively, by core needle biopsy. In one course, S- 1(100mg/day)therapy involves taking 2 courses of 14 days of administration and 7 days off the drug. Anastrozole(1mg/ day)was administered daily. After completion of one course, marked shrinkage of the axillary tumor and supraclavicular lymph node, and lightness of coughing was observed. The metastatic lymph nodes and pulmonary metastatic lesions reduced in size by over 30%, as revealed using CT. The adverse event was only grade 1 pigmentation and lacrimation. Ten months later, the self-destructed skin was completely scarred, and metastatic lesions had maintained their reduction in size. According to the results of the SELECT BC study, S-1 as primary chemotherapy for breast cancer is an evidence-based drug that can reduce the decrease in QOL, such as hair loss, and it can be positively selected.

The rate of local recurrence after mastectomy is reportedly similar to that of one-stage reconstruction. Most recurrences are in the skin or chest wall, while recurrence in the reconstructed breast is rare and the causes are uncertain. We report a case of a 42-year-old female who underwent partial mastectomy for left breast cancer with cT4aN0M1(PUL), cStage IV after endocrine therapy 3 years ago. Histopathological diagnosis was solid-tubular carcinoma. She had been treated with only endocrine therapy but diagnosed with local recurrence in the left breast. She underwent total mastectomy and rectus abdominis musculocutaneous flap reconstruction. Partial flap necrosis occurred following conservative therapy. She was accordingly treated with anastrozole and GnRH agonist. A mass approximately 1.5 cm in size was palpated inside of the reconstructed breast. As such, she was diagnosed with recurrence in the reconstructed breast through ultrasound biopsy. She underwent partial resection of the left precordial tumor, and histopathological examination revealed scirrhous cancer. She is currently well without any recurrence.

We experienced a case of locally advanced breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after endocrine therapy. A 64-year-old postmenopausal woman had a 50 mm tumor in her right breast with extensive reddening of the skin. She had axillary lymph node metastasis. Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+, PgR+) and negative HER2 status. The patient was diagnosed with locally-advanced breast cancer (cT4bN1M0, stage ⅢB). She was treated with anastrozole at a dose of 1 mg per day. The tumor decreased in size gradually and became operable after 7 months of anastrozole monotherapy. She underwent modified radical mastectomy with immediate reconstruction using a tissue expander. The resected specimen was a 30 mm tumor; adverse effects due to endocrine therapy were of Grade 1a severity. Seven months after adjuvant chemotherapy (FEC→DTX), the tissue expander was removed, and the right breast was reconstructed using an implant. No complications were noted, and the patient was treated with radiation therapy. Ten months have passed since surgery, and no local recurrence or distant metastasis has been noted.

A 69-year-old woman had undergone breast conserving surgery and axillary lymph node dissection for left breast cancer 10 years previously. The tumor was positive for estrogen receptor (ER) and progesterone receptor (PgR), and negative for human epidermal growth factor receptor-2 (HER2). Adjuvant tamoxifen and radiation therapy were administered to the conserved breast for 5 years. The patient detected a painless neck mass 1 year previously. Computed tomography (CT) revealed a hyoid bone mass, and fine needle aspiration cytology indicated a diagnosis of adenocarcinoma. Positron emission tomography combined with CT (PET-CT) revealed masses in the pelvis, spine, hyoid bone, and cervical lymph node. For definitive diagnosis, excisional biopsy of the hyoid bone was performed. Immunohistostaining revealed that the cells were CK7 (+), CK20(-), mammaglobin (+), GCDFP-15 (+), ER (+), PgR (+), and HER2 (-). The final diagnosis was multiple bone metastasis(hyoid, pelvis, spine)as well as cervical lymph node metastasis from breast cancer. After diagnosis, the patient was treated with anastrozole and denosumab, and she achieved a partial response. She has experienced progression free survival for 12 months. Metastasis to the hyoid bone is uncommon for breast cancer. We report a case in which hormone therapy was effective after it was selected based on the results of excisional biopsy.

A 76-year-old woman with a history of radical mastectomy for cancer of the right breast 38 years previously developed a solitary right lung nodule which was a metastasis from breast cancer. Diagnosis of the cause of a solitary pulmonary nodule is usually difficult in a patient with a history of extrapulmonary malignancy. A solitary pulmonary metastasis from breast cancer with a disease-free interval of longer than 15 years has been quite rarely reported. We describe an unusual case of a solitary pulmonary metastasis from breast cancer 38 years after the initial treatment.

A 75-year-old woman presented to a local doctor with a lump in the right breast. On physical examination, a tumor measuring 24mm was palpable in the BD area of her right breast. Mammography showed category 5 disease, and ultrasonography revealed a tumor measuring 24×16 mm. A mammotome biopsy provided a diagnosis of invasive ductal carcinoma of the breast(ER 7/PgR 4/HER2 1+), and the tumor was classified as stage IIA(T2N0M0)according to the UICC-TNM classification. She was recommended surgery but she rejected this option and underwent hormone therapy with anastrozole (1mg/day). One year and 8months after beginning the treatment, ultrasonography showed the tumor to measure 7.0×5.7 mm, and hormone therapy resulted in a partial response(PR). The patient hoped to undergo an operation, so she was referred to our hospital, and a right partial mastectomy and sentinel node biopsy was performed. A histopathological exami- nation indicated scirrhous carcinoma, 18mm, nuclear grade 1, f, ly1, v0, n0, ER 3/PgR 3/HER2 3+. The curative effect was grade 1a. The tumor had become HER2 positive, so the patient was then administered radiotherapy and trastuzumab and anastrozole as adjuvant therapy. Herein, we report our experience with a case of breast cancer that only became HER2 positive after hormone therapy, and also provide some bibliographic comments on this occurrence.

Here we report a case of breast cancer that recurred after a 39-year latency period. A 73-year-old woman,who had undergone radical mastectomy for left breast cancer 39 years previously,consulted our hospital complaining of lymphedema in the left arm. A computed tomography(CT)scan showed a growth of soft tissue in the left chest wall. A core needle biopsy resulted in the pathological diagnosis of metastatic adenocarcinoma,which stained positively for estrogen and progesterone receptors,but not for human epidermal growth factor receptor 2(HER2). Diagnosed with local recurrence of breast cancer, the patient was consequently treated with hormone therapy using anastrozole and achieved a partial response. The patient is currently free from further recurrent disease at 7 months. We report this late recurrence of breast cancer 39 years following mastectomy,suggesting that possible recurrence of this disease with more than a 30-year latency period should be taken into consideration.

We treated three postmenopausal female patients with unresectable local recurrence from breast cancer. All pathological diagnoses of the local recurrence lesions were ER-positive breast cancer. For treatment, we administered anastrozole to these three patients. One has been stable disease for 25 months after taking anastrozole. Another has also showed stable disease for 18 months, and the last patient has been a partial response. We performed a biopsy from a recurring lesion on these three patients, and made a diagnosis of ER-positive breast cancer. This strategy of unresectable local recurrence revealed that these three patients could have had a stable condition for a long duration by taking anastrozole.

A 69-year-old postmenopausal woman who was prescribed anastrozole for 10 months after surgical removal of her breast cancer, was referred to our hospital for acute renal failure. Because it was possible that her renal failure was related to her treatment with anastrozole, the treatment was immediately discontinued. After renal biopsy was performed to examine her renal failure, she was diagnosed as crescentic glomerulonephritis, probably related with the treatment of anastrozole. Twenty mg of oral prednisolone was administered daily after methylprednisolone pulse therapy(500 mg/day intravenous administration for three days). Her renal dysfunction was gradually improved. Renal dysfunction was considered to be a rare complication of anastrozole. Patients who are prescribed anastrozole should be watched carefully for the development of renal dysfunction.

Case: A 104-year-old female patient with a left breast mass was admitted to our hospital. Ultrasonography showed an irregular and low-echoic mass of about 2.4×2.4×1.4 cm size in the left breast EAC area. Core needle biopsy examination indicated invasive ductal carcinoma of the breast: ER (+), PR (+), and HER2 (-). An overall examination did not show a distant metastasis. We diagnosed her with left breast cancer(luminal A type) T2N0M0, stage IIA. We administered anastrozole at a dose of 1 mg/day. After 6 months, the primary tumor diameter was reduced to 2.1 cm, and the effect of anastrozole was considered a clinical partial response. The patient did not experience any adverse events during treatment. The partial response was maintained for about 2 years. We experienced a successful case of a super-elderly breast cancer patient treated with anastrozole. We conclude that hormone therapy is a useful treatment for super-elderly postmenopausal women with estrogen receptor-positive breast cancer.

We report a case of recurrent hormone receptor-positive breast cancer with brain metastases that showed good response to vinorelbine(VNR)and anastrozole(ANA). A 49-year-old woman with a history of left breast cancer had initially undergone modified radical mastectomy, but was diagnosed with lung metastases 8 years postoperatively. Despite treatment with docetaxel and tamoxifen, multiple brain metastases were detected 10 years postoperatively. To achieve prompt improvement of neurological symptoms, surgical resection was performed for two large brain foci. Stereotactic radiosurgery using a gamma- knife was applied for the remaining multiple brain metastases. Histological examination identified the brain tumors as estrogen receptor-positive, HER2-negative metastatic breast cancer. Despite the use of cyclophosphamide, adriamycin and 5- fluorouracil(CAF therapy)and capecitabine, brain metastases recurred twice along with pleuritis carcinomatosis and bone metastasis. In addition to gamma-knife re-treatment, therapy was started with VNR and ANA. All metastatic sites including brain showed a good response to therapy with few adverse reactions, and no recurrence has been observed over 3 years.

We report a 69-year-old woman with breast cancer who was effectively treated with letrozole as a second-line therapy after becoming resistant to anastrozole. Her chief complaint at presentation was back pain. Physical examination and imaging studies showed a left breast tumor with skin invasion, multiple intramammary lesions, enlarged left axillary lymph node, and multiple bone metastases. Needle biopsy revealed invasive ductal carcinoma(scirrhous carcinoma)that was ER+/PgR+/ HER2-. The administration of anastrozole and bisphosphonate for 13 months resulted in a 33% reduction of the longest diameters of the breast tumors, but a liver metastasis developed. The treatment was changed to letrozole administration from January 2007.T he optimal effect of letrozole as determined by measurement on CT images was long-term SD maintained for about 13 months. No significant side effects were observed, and the QOL was favorable.

A case was a 48 years old woman. She was aware of a lump in her left breast and visited our hospital. We diagnosed it as an invasive ductal carcinoma. Immunostaining for both ER and PgR was strongly positive. CT of the initial consultation showed multiple bone metastases (thoracic vertebrae, lumbar vertebrae, and iliac bone). After AC followed by docetaxel and tamoxifen, LH-RH analogue was started. We used anastrozole after menopause. The bisphosphonate has been used from the beginning of the treatment. After the chemotherapy, the clinical response of primary tumor was judged as partial response. For six years, the size of primary tumor has not been changed, and PET-CT has not showed another metastasis. Anastrozole was superior to tamoxifen with respect to TTP (median values of 10.7 and 6.4 months for anastrozole and tamoxifen, respectively) in postmenopausal women with ER and/or PgR receptor positive tumors. Our study indicated that many patients responding to hormonal therapy appear to have been increasing from now on.

The patient was an 86-year-old woman. In December 2005, she became aware of a tumor in her right breast at the nipple, gradually increasing in size and bleeding, and visited our department in April 2006. Roughly 3.5 cm in size, the tumor had a prominent large skin surface, bled profusely, and a dark red-colored was found at the E area of the right breast. Ultrasonography and mammography revealed that the tumor had invaded the skin and pectoralis major muscle (T4b). Core needle biopsy examination indicated invasive breast cancer (pap-tub), ER(+), PgR(+), HER2(3+). Chest CT scan and bone scintigraphy revealed swollen changes at the right axillary lymph nodes and osteoblastic changes in the 7th thoracic vertebra. We started anastrozole 1mg/day treatment. Tumor blood loss after one month was confirmed. After six months, the primary tumor size was reduced to 2 cm and the axillary lymph nodes disappeared. Administration continued about three years, and the tumor showed only the scar-like changes, and was unclear from ultrasonography (cPR). We report the long-term effect of aromatase inhibitor for elderly breast cancer patients without operation.

A case is 61 years old woman. In February 2008, she was aware of swelling, skin redness and edema in her left breast and visited our hospital. We diagnosed it as inflammatory breast cancer with positive hormone receptor (ER+, PgR+) and unexpression of HER2 (HercepTest 1 +). We started preoperative chemotherapy with weekly paclitaxel followed by FEC100, but we canceled chemotherapy because she developed cerebral infarction when we administered paclitaxel twice. Then, hormonotherapy using anastrozole (Arimidex) was therefore attempted. Three months later, treatment with anastrozole alone reduced the swelling, skin redness and edema in her left breast. After eight months of administration, the breast swelling, skin redness and edema were completely disappeared. MRI revealed the disappearance of the enhanced area. Then mastectomy with auxiliary dissection was performed.

An 83-year-old postmenopausal woman was referred to our hospital in order to get the treatment for ER positive advanced breast cancer (T4aN2M0, stage III b). The patient was diagnosed as the dissected aortic aneurysm and the hypertension. It was decided that an operation and chemotherapy would be too difficult with high existing risks. As a result, she was treated with anastrozole of PST, a 3rd-generation aromatase inhibitor, which led to the marked regression of the left breast cancer within a month. The cancer wasn't visualized after eighteen months. With the ongoing breast-hormone Therapy, no remote metastasis has been found after thirty months to this day. The patient hasn't experienced any adverse effects with the above-mentioned therapy. We concluded that the hormone (anastrozole) therapy as PST is a useful treatment for elderly postmenopausal woman with ER positive advanced breast cancer.

Recently, some new anticancer agents and hormonal agents can be used to treat breast cancer, and more patients are administering combinations of these drugs in clinical practice. Tegafur and Uracil (UFT) have been widely used for the postoperative chemotherapy of breast cancer, and often combined with hormonal agents. However, due consideration has not been given to safety and compliance of the combined use of UFT and aromatase inhibitor (AI). We therefore studied the safety and compliance with UFT alone and in combination with the hormonal agents tamoxifen or anastrozole as postoperative therapy in postmenopausal women with breast cancer. Our results confirmed that longterm postoperative therapy with UFT alone was feasible, provided that early adverse events are carefully monitored. Combined therapy was not associated with a significant increase in the incidence of adverse events or a decrease in compliance, even in older adult patients. Therefore, we consider UFT plus a hormonal agent (especially anastrozole) to be a treatment option for patients with HER2-negative highly or incompletely endocrine responsive disease who require relatively moderate chemotherapy or for older adult patients who require treatment with low toxicity.

We report an 89-year-old patient with recurrent hormone-responsive breast cancer who presented with pleural, skin and bone metastases. Nineteen years previously, she had undergone a mastectomy and then for 16 years received adjuvant hormone therapy. The patient was orally administered a combination therapy of anastrozole, UFT and cyclophosphamide. A remarkable response was seen after 5 months, and no side effects were observed. The patient became well and the treatment was continued without relapse at 8 months. Oral anti-cancer treatments in combination with hormone therapy appear to have few side effects and might be an effective treatment option for recurrent breast cancer patients.

The patient was a 56-year-old female. At the age of 35 years, she had under gone left mastectomy and axillary lymph node dissection for breast cancer. After surgery, hormonal therapy was continued for 3 years. Then, no treatment was performed. In this study, single therapy with an AI agent was started to treatbilateral supraclavicular fossa/mediastinal lymphnode metastases. After 6 months, a partial response(PR)was achieved. However, progression of the disease(PD)was noted after 1 year. Thereafter,the regimen was switched to single high-dose(120mg/day)TOR therapy. CT revealed the disappearance of the bilateral supraclavicular fossa lymphnodes and a marked reduction of the other lymphnodes. Currently, the patient is being treated, with an interval of 10 months from the start of TOR therapy.

A 51-year-old postmenopausal woman was referred to our hospital for treatment of ER-positive recurrent breast cancer. The patient had lung and pleural metastases with pleural effusion from breast cancer. She was treated with anastrozole, a 3rd-generation aromatiase inhibitor. The efficacy of the treatment was definite: the multiple metastatic lung lesions showed a partial response after 5 months' treatment, and reached a complete response after 14 months' treatment. The patient experienced no adverse effects with this therapy. Anastrozole therapy is a useful treatment for postmenopausal woman with ER-positive recurrent breast cancer.

An 85-year-old postmenopausal woman had multiple lesions in her right breast. Core needle biopsy showed solidtubular carcinoma with positive hormone receptor (ER+++, PgR-). She refused surgery and was then treated with anastrozole as neoadjuvant endocrine therapy. After seven months of the treatment, all lesions were increased or unchanged. The clinical response was judged as stable disease. Letrozole was chosen for the next therapy. After ten months, reductions in the tumors were noted, and the clinical response was judged a partial response. No side effects were observed. These two drugs are nonsteroidal aromatase inhibitors, and it is considered there is a cross-resistance between them. However, several studies have revealed letrozole was significantly more potent than anastrozole in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in vivo. This may be related to a difference in effect between the two drugs. It is suggested that letrozole as second-line endocrine therapy may be effective for postmenopausal breast cancer even after anastrozole failure.

Background: There are three third-generation aromatase inhibitors (AI) available in Japan. Though it is supposed that they can be administered sequentially because of their little cross-resistant effect, it is not definite which sequential treatment is best., Purpose: To examine retrospectively the difference in efficacy by the AI sequence when anastrozole ( ANA) and exemestane (EXE) are clinically administered sequentially for patients with metastatic breast cancer., Patients: We examined 22 patients with metastatic breast cancer administered ANA alone as first-line AI treatment, EXE alone as second-line (A--> E group), and 13 patients given EXE alone as first-line AI treatment (E --> A group) since December 2002 in our hospital., Method: In the A --> E and E --> A group, we examined overall response rate, clinical benefit (CB) rate, time to progression (TTP) for the first- and second-line treatment, respectively, overall survival (OS) after starting AI and successive efficacy of the two AIs., Results: There were no significant differences between the two groups in patient characteristics and history of prior treatments. Overall response rate of the first-line treatment in the A--> E and the E--> A group was 31.8% and 38.5%, and the CB rate was 68.2% and 53.8%, respectively. Overall response rate of the second-line treatment in the A --> E (22 cases) and the E --> A (3 cases) group was 13.6% and 0%, and the CB rate was 36.4% and 33.3%, respectively, reflecting no particular differences. In the A --> E group, five (33.3%) among 15 cases obtained CB by EXE and three (42.6%) among 7 cases who did not obtain CB by ANA did so by EXE. Also, in the E--> A group, one among 3 cases who did not obtain CB by EXE did so by ANA. No significant differences were observed in TTP and OS between the two groups., Conclusion: When ANA and EXE are administered sequentially, no particular difference in efficacy occurs due to the sequence. In some cases, 2 agents become effective successively, and cases resistant to first-line treatment can expect efficacy from second-line treatment. Sequential treatment with the two agents seems to provide very significant efficacy in clinical practice regardless of the order of administration.

A 47-year-old woman was admitted to our hospital for advanced breast cancer with multiple liver metastases and liver dysfunction in January 2004. EC (EPI combined with CPA), weekly PTX, and AI were performed but were not effective for that tumor. Therefore, high-dose TOR was started. Liver dysfunction recovered after administration of TOR, and primary tumor and liver metastases were evaluated as a partial response (PR). The same therapy has been performed for six months with no evidence of deterioration.

An 81-year-old woman with a right breast tumor exposed through the skin surface visited our clinic in June 2004. Pathological findings of the resected tumor specimen indicated invasive ductal carcinoma of the breast,positive ER/PgR status,and negative HER 2/neu status. The enlarged right axillary lymph nodes were palpable. Ultrasonography and computed tomography revealed that the tumor invaded the chest wall without any metastasis to remote organs. On July 5, 2004, we started anastrozole treatment. Its effects were confirmed in the first month,and the treatment was continued for 8 months. Substituting anastrozole with exemestane was not effective. However, the exposed part of the tumor completely responded to tamoxifen that was administered for 2 months. The effect of tamoxifen continued until February 2006, and most of the subcutaneous part of the tumor became nonpalpable. Thus, sequential endocrine monotherapy proved useful for an elderly woman with locally advanced breast cancer.

We report two patients having recurrent breast cancer with brain metastases that was controlled well with a gamma knife radio-surgery. The patient is a 50-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy, and extended right lobectomy of the liver were performed in December 2001. Afterward, pleurodesis was carried out to the carcinomatous pleurisy. Then she underwent simple total hysterectomy and bilateral oophorectomy for torsion of the metastatic ovarian tumor. MRI study revealed brain metastases with a diameter of 1 cm in her right midbrain in April 2005, so a gamma knife radio-surgery was performed. After the radio-surgery, a weekly paclitaxel therapy followed by peroral chemotherapy with capecitabine was started, and she took the regimen continuously. Another patient is a 56-year-old woman. She underwent skin sparing mastectomy with axillary lymph node dissection for right breast cancer in November 2002. Metastases to the base of her skull were found in October 2004, so a gamma knife radio-surgery was carried out. After the radio-surgery, a weekly paclitaxel therapy with anastrozole was started. In both of the two patients, the metastatic brain tumors have not shown growth so far and are under good control as of March 2006.

A 73-year-old postmenopausal woman had a 13 cm-sized huge tumor in her left breast with an extensive purple skin color change. She had sternal destruction, axillary and supraclavicular lymph node metastases (T4bN3M1, Stage IV). Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+++, PgR+++). She was treated with 1 mg per day of anastrozole. The tumor decreased in size gradually and became operable after 7.5 months of the anastrozole monotherapy. She underwent mastectomy and axillary node clearance. The resected specimen showed a 3.5 cm sized tumor with significant fibrosis and scanty viable tumor cells. We concluded that neoadjuvant therapy with anastrozole is a good choice for receptor-positive postmenopausal breast cancer, especially for elderly or poor risk women.

We report three cases with advanced breast cancer were treated with a weekly dose of paclitaxel (TXL). Case 1: A 52-year-old female, diagnosed as having bilateral breast cancer with metastatis to right lung (S9) and sternum. A TXL weekly regimen was started (80 mg/m2 with the administration of the drug for three weeks followed by one week rest as one course). After twelve courses of treatment, bilateral breast masses significantly regressed with the disappearance of bilateral axillary and parasternal lymph node metastasis. The tumor marker was normalized, too. After two years and four months, the patient is still alive and continuing the weekly TXL regimen. Case 2: A 51-year-old female with right breast cancer and skin ulcer formation. After completing two courses of weekly TXL regimen, her mass was markedly reduced in size, which made it possible for her to undergo a modified mastectomy. Case 3: A 52-year-old female with breast cancer which invaded the skin. As a result of two courses of weekly TXL therapy, the tumor responded significantly and a modified mastectomy was conducted. The TXL weekly regimen seems to be very effective in regressing breast tumors and can be given safely in the outpatient setting with an extremely high utility profile as neoadjuvant chemotherapy as well.

A 46-year-old woman who had received mastectomy for breast cancer 6 years earlier complained of abdominal distension. Computed tomography and ultrasonography revealed massive ascites and ovarian swelling of both sides. She was diagnosed as having primary ovarian cancer and peritoneal dissemination, and underwent a total hysterectomy as well as ovarectomy on both sides. After surgery, she received a sequential chemotherapy, ie, intraabdominal injection of carboplatin (CBDCA 300 mg/m2) and div administration of paclitaxel (PTX 180 mg/m2) as a standard regimen for advanced ovarian cancer. However, detailed histological examinations showed that the ovarian cancer had metastasized from her breast cancer. It is well-known that breast cancer easily metastasizes to the bone, liver, pleura and lymph node, but rarely to the ovarium or peritoneum when chemotherapy is conducted. Therefore, no standard therapy has been established for breast cancer metastasizing to the ovarium. Our patient received 4 cycles of weekly administration of PTX (PTX 80 mg/m2, 3 consecutive weeks, 1-week break), followed by oral administration of doxifluridine+anastrozole on an outpatient basis. No evidence of recurrence of breast cancer has been noted 1 year after surgery. This result suggests that weekly administration of PTX and intraabdominal injection of CBDCA might be beneficial in the treatment of recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation.

We describe a postmenopausal woman suffering from advanced breast cancer with pleural effusion. She had prior anastrozole therapy, and was referred to our hospital with dyspnea. The use of exemestane, a highly selective steroidal aromatase inhibitor (25 mg daily), successfully induced remission of pleural effusion. Exemestane is a useful treatment for postmenopausal woman with advanced breast cancer, which is refractory to anastrozole.

We reviewed therapeutic effects and harmful side effects in 33 patients with advanced or recurrent breast cancer who underwent treatment with Anastrozole 1 mg/day in our department. The patients ranged in age from 40 to 83 years old (median, 59). The Performance Status was 0-2, and there was 1 case of advanced breast cancer and 32 cases of recurrent breast cancer. The duration of disease was from 5 to 233 months (median, 50 months). The estrogen and/or progesterone receptor-positive rate was 72.7%. Metastatic sites were in multiple organs in 9 cases, in the lung only in 1 case, in bone only in 12 cases, and in soft tissue only in 10 cases. First-line therapy was used in 10 cases, second-line therapy in 6 cases, and above third-line therapy in 17 cases. There was a complete response in 3 cases, partial response in 5 cases, no long change in 13 cases, no change in 9 cases, and progressive disease in 3 cases. The response rate was 24.3%, The response period ranged from 2 to 22 months (median, 8 months), and clinical benefit was achieved in 63.7%. The clinical benefit rates for first-line were 60%, second-line 83.3% and above third-line therapy 58.8%. The response rate for patients with breast cancer resistant to Anthracyclines and/or Taxanes was 20%. Time-to-progression ranged from 2 to 28 months (median, 11 months), and overall survival ranged from 7 to 30 months (median, 15 months). The most frequent harmful side effects were rise in total cholesterol, general fatigue, hot flashes and arthralgia (9.1%). In this study, we confirmed the availability and safety of Anastrozole, which was suggested to be a useful drug in salvage therapy for patients having resistance to Anthracyclines and/or Taxanes, not only but also useful as a first- or second-line therapy.

For metastatic breast cancer patients who have hormone receptor-positive tumors, hormonal therapy aiming at optimal palliation and prolongation of life is the initial treatment of choice. To enhance the effect of hormonal monotherapy, a combination therapy with Anastrozole 1 mg po and 5'-DFUR 800 mg po daily was given to 11 patients with metastatic breast cancer. At a median follow-up period of 15 months, the overall response rate was 45.5%. The median duration of response in responders was 25 months. The overall median survival for the entire series was 15 months after the start of treatment. No patients complained of adverse events of grade 2 and over. This combination therapy with good response and little side effects is useful for metastatic breast cancer patients.

Major advances have been made in the treatment of postmenopausal women with hormone-sensitive breast cancer. Although tamoxifen has been the standard endocrine therapy for the past twenty years, the development of a third generation of aromatase inhibitors (Als), which effectively inhibit estrogen synthesis in extragonadal sites, gives us a wider range of choices in endocrine therapy. However, many questions remain with respect to the optimal use of Als. Differences between Als and tamoxifen as well as non-steroidal and steroidal Als in their long-term adverse effects on bone demineralization and lipid metabolism are only starting to emerge. The preferable orders for use of non-steroidal and steroidal Als, Als and pure anti-estrogen in patients with metastatic disease are emerging subjects to be examined, following several studies that showed non-cross reactivity between these types of drug. Neo-adjuvant endocrine therapy is now attempting to apply breast conserving surgery in larger numbers of elderly patients who are not suitable for neo-adjuvant chemotherapy. Moreover, many investigators are currently searching for surrogate markers in neo-adjuvant endocrine treatment that can predict the responsiveness and prognosis with adjuvant endocrine therapy. Further research concomitant with clinical trials may lead to a more reliable endocrine therapy modality in the treatment of breast cancer.

A 52-year-old female underwent radical mastectomy at the age of 41 for left breast cancer (n0, positive for ER). After a few years of adjuvant TAM therapy, follow-up was stopped at the age of 50 with no recurrence. She had suffered from symptoms of cold since January 2001 and came to our hospital complaining dyspnea on February 11. CXP showed pleural effusion of the entire thoracic cavity and she was admitted to the hospital immediately. Pleural exudate cytodiagnosis showed carcinomatous pleurisy; however, dyspnea and thoracic effusion were improved by continuous thoracic drainage and instillation therapy. Various examinations demonstrated that the carcinomatous pleurisy was due to recurrent breast cancer. They also showed local recurrence, left supraclavicular lymph node metastasis and multiple bone metastasis. Thus, combined chemoendocrine-therapy of CTF (CPA, THP and 5-FU) and anastrozole was administered. After 6 cycles of CTF, the carcinomatous pleurisy, local recurrence and left supraclavicular lymph node metastasis were diagnosed as CR by CXP, chest CT and US and multiple bone metastasis were diagnosed as PR by bone scintigram. The patient continues to be treated on an outpatient basis with no recurrence about one year after the beginning of the treatment (6 months after CTF 6 cycles) and she is taking anastrozole continuously.

A 63-year-old postmenopausal woman was referred to our hospital for treatment of ER positive advanced breast cancer. The patient had lung and pleural metastases with pleural effusion from breast cancer. She was treated with anastrozole, a 3rd-generation aromatase inhibitor, which brought about a marked regression of the lung tumor, and disappearance of pleural effusion. The patient experienced no adverse effects with this therapy. Anastrozole therapy is a useful treatment for postmenopausal women with ER positive advanced breast cancer.

Endocrine therapy for breast cancer, which began with ovariectomy, has a history of more than 100 years. Tamoxifen has been an epoch-making drug during the late 20th century. Recently LHRH analogues which work as downregulators of estrogen production and many aromatase inhibitors (AI), both non-steroidal and steroidal have been developed in Japan. Fadrozole was the only AI until anastrozole was approved a few months ago. Letrozole was shown to be a better AI than fadrozole by prospective randomized double blind examination; however, it is not licenced yet. The reason is that the appropriate dosage is not identical to that of Western countries. We have reached a time when order-made medicine should take into consideration such differences as race and individuality.

Anastrozole (JAN), developed by Zeneca UK (presently AstraZeneca UK), is a new aromatase inhibitor which belongs to triazole. Anastrozole shows selective aromatase inhibition and negligible effects on other steroid hormone biosyntheses. The daily dose of 3 mg/kg anastrozole inhibited the growth of DMBA mammary tumours significantly. Anastrozole inhibited the tumor growth at 5 micrograms/mouse/day (s.c.) in androstenedione-treated ovariectomized nude mice inoculated with MCF-7CA cells transfected with aromatase gene. In the Japanese Phase IIa study, the response rate was 27.8% (10/36) in the 0.5 mg group, and 38.2% (13/34) in the 1 mg group. The most common adverse drug reactions were leucopenia in the 0.5 mg group, and LDH increased and leucopenia in the 1 mg group. There were no early deaths, other serious adverse events, or adverse drug reactions of grade 3 or above in this trial; anastrozole was well tolerated. In the Japanese Phase IIb study, the response rates were 33.3% (117/351 patients) and 32.8% (114/348 patients) for anastrozole and tamoxifen, respectively, showing non-inferiority of anastrozole. The median time to disease progression (TTP) was 251 days and 252 days for anastrozole and tamoxifen, respectively. Group comparison using a Cox regression model revealed non-inferiority of anastrozole. Therefore, anastrozole was found to be at least as effective as tamoxifen (in the response rate and TTP). In US study compared anastrozole with tamoxifen, TTP with anastrozole is a significantly longer than that of tamoxifen (p = 0.005, two-sides). Anastrozole has shown to be at least as effective as tamoxifen, standard endocrine therapy for breast cancer, with good safety profiles. Thus, anastrozole is a promising first-line endocrine therapy in the treatment of postmenopausal breast cancer.

Standard adjuvant chemo/endocrine therapy for breast cancer patient is based upon St. Gallen's consensus 1998. Recent development in the field of adjuvant chemo/endocrine therapy is an usage of LH-RH analogue with tamoxifen for premenopausal hormone receptor positive women, and also an emerging role of taxans. Orally given 5-FU derivatives may work in adjuvant settings. The third generation aromatase inhibitors have established their role in second line hormone therapy for the advanced or recurrent breast cancer patients. High dose chemotherapy should not be used in outside clinical trials.