Two cases of effective weekly paclitaxel administration for metastatic breast cancer]

We report two cases of effective weekly paclitaxel (TXL) administration for metastatic breast cancer. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. Case 1: A 66-year-old woman was treated with adriamycin, cyclophosphamide, doxifluridine (5'-DFUR), fadrozole, medroxyprogesterone acetate (MPA) and pamidronate for pleural, mediastinal and supraclavicular lymph nodes and skull metastases. She complained of hoarseness and supraclavicular and mediastinal lymph nodes had developed, for which she received weekly TXL administration. Metastatic lymph nodes had disappeared 3 months after administration. Case 2: A 61-year-old woman was treated with CMF therapy, 5'-DFUR, tamoxifen, MPA fadrozole and pamidronate for bone metastasis and local recurrence. She received weekly TXL administration for an axillary recurrence and contralateral supraclavicular lymph node metastases. Metastatic and recurrent lesions had disappeared 3 months after administration. The toxic events were leukopenia (grade 1) and peripheral neuropathy (grade 1). No major adverse effects were observed in either case.     

A case of effective bisphosphonate therapy of sequential pamidronate and incadronate for bone metastases from breast cancer

A 55-year-old woman complained of neck pain ten years after undergoing surgery. She was diagnosed as having bone metastases and treated using pamidronate therapy with doxifluridine, tamoxifen and fadrozole, which was assessed as effective. She complained of neck pain 32 months after pamidronate infusion. CT revealed that the sclerosis had continued but new lytic lesions were detected in the cervical vertebra. Thus, we attempted incadronate and medroxyprogesterone acetate (MPA) administration. After 2 months, incadronate therapy with MPA relieved her neck pain. CT revealed lytic lesions of cervical vertebra showing sclerosis 3 months after this treatment and the sclerosis has continued. Bisphosphonate therapy of sequential pamidronate and incadronate with MPA administration is a useful treatment for bone metastasis from breast cancer.     

Two cases of radiofrequency ablation (RFA) therapy for control of liver metastases from breast cancer

We present two cases of liver metastases from breast cancer treated by radiofrequency ablation (RFA) for elongation of life. Case 1: A 50-year-old woman was treated by left mastectomy (stage IIIa) in December 2002. In April 2004, she was treated with a combination therapy of weekly paclitaxel and trastuzumab for multiple liver metastases, left supraclavicular lymph node metastases, and multiple bone metastases. After 16 courses of weekly paclitaxel and trastuzumab, liver metastases decreased significantly in size. Because liver metastases recurred during a continuation of weekly paclitaxel and trastuzumab, we performed RFA and chemotherapy using a hepatic artery infusion of docetaxel for liver metastasis. The aggravation spread to the liver lesion and she died after 20 months from liver metastases. Case 2: A 65-year-old woman was treated by left mastectomy (stage IIA) in 1984, and the distant metastasis was not found through the course after an operation. She was noted with a liver function aberration in another hospital in March 2005. We scanned it, and it was diagnosed as multiple liver and bone metastases from breast cancer. Because she did not hope for an anticancer drug treatment for multiple liver metastases, we performed RFA in May 2005. After the second RFA was performed, she does not show any new lesion to the liver for 10 months.     

Therapy-related acute promyelocytic leukemia caused by hormonal therapy and radiation in a patient with recurrent breast cancer

We report a patient with therapy-related acute promyelocytic leukemia (APL) that may have been caused by regional radiation or hormonal therapy after surgery. A 36-year-old Japanese woman developed right breast cancer and underwent breast-conserving surgery and regional radiation to the right breast without adjuvant systemic therapy because she wished to preserve her fertility. Two years later, she developed multiple bone metastases of breast cancer and received hormonal therapy. During the second line hormonal therapy, she developed APL and received induction and consolidation chemotherapy with all-trans retinoic acid (ATRA) and a combination of anthracycline and cytarabine. After she achieved a complete remission (CR) of the APL, her bone metastases of breast cancer progressed. She received weekly paclitaxel treatments and her bone marrow function recovered. However, 9 months later, her APL relapsed; she achieved a second CR after undergoing ATRA therapy again. This patient is thought to be a rare case of secondary leukemia, since the leukemia might have been caused by hormonal therapy and regional radiation without chemotherapy.     

Two cases of choroidal metastasis from breast cancer

We report two cases of choroidal metastasis from breast cancer. The first case was a 41-year-old woman with loss of her right upper visual area in whom right breast cancer accompained by lung and choroidal metastases were detected simultaneousyl. She died without having received radiation therapy for the affected eye 6 months after mastectomy and oophorectomy. The second case was a 34-year-old woman in whom choroidal metastasis causing right visual disturbance was diagnosed 3 years after mastectomy for breast cancer. She received radiation therapy following oophorectomy and her visual acuity completely recovered. She dies 7 months later. Radiation therapy improved her quality of life despite her short survival, because her visual acuity was maintained until death. In general, the life span of patients with choroidal metastases is short because of multiple organ metastases, but to obtain a better quality of life, active treatment of the affected eye is necessary.     

Two cases with long-term disease-free survival after resection and radiotherapy for solitary brain metastasis from breast cancer with extensive nodal metastases

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.     

A case of recurrent breast cancer with multiple liver metastases responding to combination therapy of capecitabine and MPA

The patient was a 68-year-old woman who underwent left partial mastectomy on February 1999. The stage was T2N1. There were positive for estrogen and progesterone receptors in the tumor. After operation, adjuvant therapy consisting of oral administration of tamoxifen and radiation was performed. On February 2005, she felt dyspnea and right femoral pain. After examinations, she was diagnosed as recurrent breast cancer with pleuritis carcinomatosa and bone metastasis. The patient was treated with oral administration of anastrozole and pamidronate disodium 90 mg intravenously every 4 weeks, radiation of her right femur, and OK-432 injection into the intrapleural cavity. On November 2005, she felt general fatigue and anorexia. CT examination revealed multiple liver metastases. She was treated with oral combination chemoendocrine therapy with capecitabine (2,400 mg/day) and MPA (600 mg/day). After the four courses, multiple liver metastases were remarkably reduced in the CT findings. After twelve courses, the partial response continued. No adverse reactions occurred except for gain in weight of grade 1. It is suggested that this oral combination chemoendocrine therapy may be useful for recurrent breast cancer with consideration for treatment effectiveness and the quality of life of the patient.     

A case of multiple bone metastases from advanced breast cancer effectively treated with pamidronate]

A 57-year-old woman, with bone, lymph node and skin metastases underwent mastectomy and extirpation of skin tumors. Chemoenderine-therapy was performed from the 15th day after operation, with a toremifene and CEF regimen consisting of cyclophosphamide, epirubicin and 5-fluorouracil. She had nausea and neurological symptoms from hypercalcemia (21.5 mg/dl) on the 28th day after operation. Her serum PTHrP level was found to be high at 214 pmol/l. We administered pamidronate in a dose of 45 mg biweekly, and she improved. The CEF regimen and pamidronate therapy was continued for 6 cycles and the regions of bone metastases were reduced on the bone scintography. Thereafter she has been administered pamidronate 30 mg/4 weeks as an outpatient with no further symptoms, and serum Ca and PTHrP have remained normal. In conclusion, pamidronate combined with chemotherapy can be a therapeutic option for not only hypercalcemia but also bone metastases of breast cancer.     

A case of recurrent breast cancer with bone marrow metastasis treated with weekly paclitaxel therapy

A 44-year-old woman with bone marrow metastasis from breast cancer was treated with weekly paclitaxel therapy. She underwent radical mastectomy for right breast cancer (T2N1M0, Stage II B) in April 2003, and was then treated with hormonal therapy (leuprorelin). In November 2005, she received radiation for bone metastasis in thoracic and lumbar vertebrae, and bisphosphonate therapy was performed. Additional hormonal therapy (tamoxifen) was administered for progressive bone metastasis. However, in September 2006, pancytopenia was recognized and bone marrow metastasis was diagnosed by bone biopsy. Disseminated intravascular coagulation (DIC) developed, so she was given weekly paclitaxel therapy with blood transfusion and G-CSF injection. Improvement of pancytopenia and tumor markers was recognized temporarily, and but 3 months later the tumor markers increased again. Four months after introduction of chemotherapy, she died of gastrointestinal hemorrhage.     

A case of breast cancer with multiple bone metastases improved by high-dose toremifene]

A 63-year-old woman underwent modified radical mastectomy with 3 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, 5-fluorouracil) and MPA endocrine therapy for breast cancer. Because of nausea and general fatigue, she refused to continue this therapy and did not visit the hospital. When she came our hospital and 16 months later, she had developed multiple bone metastases. At the same time, she was suffering from lung tuberculosis. She was treated with toremifene at a dose of 120 mg/day without any side effects. After 3 months administration of toremifene, pain disappeared and her high serum CA15-3 and BCA225 dropped to within the normal range. On bone scintigrams, abnormal accumulation almost disappeared after 9 months of administration of toremifene. In this case, the patient was suffering from lung tuberculosis and did not desire intensive chemotherapy. Administration of high-dose toremifene was effective for multiple bone metastases without any side effects.     

A case of adriamycin and methotrexate-resistant recurrent breast cancer treated with doxifluridine and mitomycin C]

A 49-year-old woman was diagnosed with local recurrence and cervical lymph node and bone metastases 55 months after surgery for breast cancer. She was treated with goserelin acetate and tamoxifen but the disease was assessed as progressive after 8 months. Five courses of CMF therapy were performed but lung, pleural and mediastinal lymph node metastases were detected. Then, five courses of CAF therapy were carried out, but a contralateral breast metastasis was detected and the patient complained of shortness of breath. The CAF therapy was assessed as PD. We attempted administration of doxifluridine (5'-DFUR) and mitomycin C (MMC) on an outpatient basis. After 6 months, no progressive disease was detected and she was relieved of her shortness of breath. The combination therapy was assessed as long NC. Combination therapy with 5'-DFUR and MMC is thus a useful treatment for adriamycin- and methotrexate-resistant breast cancer, especially in terms of quality of life.     

Pain relief with alendronate therapy in a breast cancer patient with bone metastasis

A 66-year-old woman developed a bone metastasis from breast cancer to the sternum in September, 1997. She received alendronate therapy, consisting of biweekly intravenous administrations of 10 mg-alendronate 6 times and monthly 20 mg-alendronate infusions 15 times. The first alendronate administration markedly alleviated her bone pain. She obtained complete pain relief after the 4th alendronate infusion. However, an elevation of tumor marker levels in serum without any pain increase forced us to treat her with medroxyprogesterone acetate and doxifluridine in addition to the alendronate therapy. With these therapies, she has shown an objective response (PR) of the bone metastasis for 8 months. In conclusion, alendronate therapy was effective against bone pain due to metastasis of breast cancer.     

Remarkable improvement in a patient with metastatic and locally advanced HER2-positive breast cancer treated with trastuzumab plus vinorelbine

A 39-year-old premenopausal nulliparous woman presented with severe pain in her right breast, bleeding and pus-like discharge, and a deep ulcer approximately 18 cm in diameter.Contralateral breast metastasis, bilateral axillary lymph node metastases, and multiple lung and bone metastases were detected on computed tomography.Five years previously she had undergone surgery for ovarian cancer and had prematurely discontinued adjuvant chemotherapy because of side effects. Following the administration of pain control, the patient received trastuzumab(Tr)plus vinorelbine(VNR)for her breast cancer as first-line therapy to avoid hair loss.The ulcer on her right chest wall underwent complete epithelialization and the patient's performance status improved from 3 to 0.The pus-like discharge, pain, bleeding, and odor from the breast resolved completely, and 5 months later, her quality of life had improved.The lung metastases also resolved completely.No adverse affects, including hematotoxicity and hair loss, were seen until treatment failure 12.5 months later. Second-line and third-line treatments were performed, but brain metastases developed, and the patient's overall condition deteriorated because of the development of ileus of unknown etiology.She died 21 months later.The patient received all therapies on an outpatient basis. Combination therapy using Tr and VNR is superior in safety and tolerability, and has been considered an option for first-line treatment of metastatic, locally advanced HER2-positive breast cancer.     

A case of HER2-positive metastatic breast cancer responding to trastuzumab plus gemcitabine combination therapy

A 60-year-old woman was admitted to the hospital with left thigh pain. She had undergone mastectomy and axillary lymph node dissection for right breast cancer (T3N2M0) five years and two months earlier. The pathological diagnosis then was invasive ductal carcinoma with axillaryly mph node metastases. Hormone receptors and HER2 status were negative and positive (3+), respectively. The patient received adjuvant chemotherapy and radiotherapy, but bone metastases appeared 18 months after surgery. Although trastuzumab-combination chemotherapy with taxane and/or capecitabine was given, bone metastases in thoracic vertebra resulted in incomplete paralysis in both legs. She underwent thoraco-lumbar vertebral fixation 10 months before admission. A PET/CT revealed multiple bone metastases in the left femur as well as vertebrae, and CEA rose markedly. She received radiotherapy and trastuzumab monotherapy in addition to bisphosphonate. Temporarily, CEA decreased, but because recurrence nests were recognized in the supraclavicle and mediastinum after the eight-month treatment, trastuzumab monotherapy was followed by trastuzumab plus vinorelbine combined therapy. This regimen markedly reduced CEA after three months, but it rose again over the following three months. As S-1-combined therapy was not effective, trastuzumab+gemcitabine (1 g/week and two weeks on/one week off) combined therapy was started. CEA decreased markedly after 4 cycles, and FDG accumulation in the recurrence region was markedly improved. The adverse event during this treatment was minor, and PS was sufficiently maintained. These results suggest that trastuzumab plus gemcitabine combination therapy is effective for HER2-positive metastatic breast cancer.     

A case of breast cancer with multiple bone metastases demonstrating complete remission with high-dose toremifene therapy

We report a 64-year-old woman who underwent mastectomy for stage II (T2N1M0) advanced breast cancer, in whom multiple spine metastases developed 18 months postoperatively. She received 6 cycles of CA (cyclophosphamide 500 mg/m2, ADM 50 mg/m2 3 wq) therapy and oral tamoxifen (20 mg/body) administration for adjuvant therapy. The multiple bone metastases of the spine were revealed by technetium bone scan. The level of serum tumor marker CA15-3 increased two times over the normal range 18 months after surgery. She also developed osteoporosis a few years later, so we selected high-dose toremifene administration (120 mg/body) as a second-line therapy. No adverse effects have occurred and bone metastases disappeared. Moreover, the tumor marker was also normalized 6 months after toremifene therapy started. It was shown that high-dose treatment of toremifene was useful for recurrent breast cancer with bone metastasis.     

A case of long-term survival of liver metastasis of breast cancer successfully treated with chemotherapy and endocrine therapy

A 42-year-old woman was diagnosed as having hepatic metastasis two years after radical mastectomy for breast cancer. She was initially treated with oophorectomy and cytotoxic chemotherapy, which resulted in complete regression of the lesion within two years after the start of the treatment. She remained free of the disease until the fifth year thereafter, when she again developed a metastatic lesions in her liver. Since then, she has been treated sequentially with various kinds of chemotherapy and endocrine therapy with a certain degree of response to each treatment. She has survived 12 years and three months after the development of liver metastasis. This patient is the longest survivor of hepatic metastasis from breast cancer in the Japaneses literature.     

A case of osteonecrosis of the jaw in a breast cancer patient with bone metastases receiving long-term treatment with bisphosphonates

Bisphosphonates (BPs) are often used for the treatment of several diseases such as osteoporosis, cancer-associated hypercalcemia, and osteolytic bone metastasis. Recently, there have been reports of osteonecrosis of the jaw (ONJ) in cancer patients whose treatment regimens include BPs. In this case report, we describe complications and treatment of ONJ in a breast cancer patient with bone metastases who received long-term treatment with BPs. A 70-year-old woman underwent modified radical mastectomy on her left breast cancer and received oral 5-fluorouracil derivatives for 2 years in another hospital. Eleven years after the surgery, she came to our hospital complaining of spinalgia and was diagnosed with recurrent breast cancer with multiple metastases to the stomach, liver, multiple lymph nodes, and spine. After surgery for spine metastases, she was given a combination therapy of trastuzumab (initial bolus: 170 mg/body, followed by two or more cycles of 85 mg/body) every week, docetaxel (100 mg/body) every 3 weeks, and BPs (90 mg/body) every 4 weeks. About 1 year and 4 months later, she complained of pain in her right maxilla; biopsy revealed ONJ. Medical oncologists need to recognize ONJ as a serious side effect of BP treatment; dentists and oral and maxillofacial surgeons need to thoroughly consult patients regarding the administration of BPs and have them make an informed consent.     

A patient with of metastatic breast cancer with a well-controlled quality of life using S-1 therapy as first-line chemotherapy

We experienced a case of endocrine therapy-resistant recurrent breast cancer with liver and bone metastases, treated with S-1 as first-line chemotherapy and maintaining a good quality of life. The patient was a 31-year-old premenopausal woman. She was diagnosed with cancer of the left breast(T1(18mm), N0, M(-))and underwent breast-conserving surgery, sentinel lymph node biopsy, and radiation therapy in August 2002. As there was hormone sensitivity, she was treated with LHRH analog for 3 years and tamoxifen for 5 years as adjuvant therapy. After her first childbirth, she had a recurrence of liver and bone metastases. After treatment with endocrine therapy failed, an oral administration of S-1 was initiated as first-line chemotherapy considering her QOL. She received 8 months of S-1 therapy with no severe adverse reactions and maintained a high quality of life. Treatment with S-1 is thought to be useful for first-line chemotherapy if the treatment demonstrates a therapeutic equivalence with taxane on patients' overall survival.     

Two cases of breast cancer markedly responded to neoadjuvant chemoendocrine therapy (2 cycles of CMF and tamoxifen, pCR and near pCR)

Case 1 is a 38-year-old woman with a 6 cm tumor in her right breast. After incisional biopsy she received 2 cycles of CMF and tamoxifen in order to effect down staging. The tumor markedly decreased in size. She next underwent breast conserving surgery. Histopathologically, malignant cells completely disappeared (pCR). Case 2 is a 34-year-old woman with a 5.5 cm tumor in her left breast. After incisional biopsy she received the same regimen as in case 1. The tumor diminished significantly in size, and she underwent breast conserving surgery. Histopathologically, only a few fragments of degenerated tumor cells remained. Case 1 was hormone receptor positive, while case 2 was negative. The remarkable responsiveness (pCR and near pCR) to 2 cycles of CMF combined with tamoxifen was interesting. From these results we conclude that the CMF regimen is an useful neoadjuvant chemotherapy alternative to avoid alopecia and GI tract side effects.     

A case of metastatic breast cancer responding to weekly paclitaxel and high-dose toremifene administrated alternately

A 64-year-old woman underwent muscle-preserving mastectomy for breast cancer in April 1999. She developed multiple lung metastases 3 months later. The metastases partially responded to 10 cycles of CAF (cyclophosphamide, adriamycin, 5-fluorouracil). However, her lung metastases worsened again 7 months later and CAF was not effective (progressive disease). We therefore began administration of low-dose paclitaxel (80 mg/m2/week) and high-dose toremifene (120 mg/day) alternately in April 2001. This alternative therapy brought a marked decrease in the lung metastases. After 4 cycles of this treatment, lung metastatic findings had disappeared from her chest X-ray. This alternative therapy is potentially effective against metastatic breast cancer.