Lactic acidosis. A presentation of metastatic breast cancer arising in pregnancy.

Lactic acidosis B is a rare metabolic complication of malignancy. It usually is associated with advanced and extensive metastatic disease. The authors report a case in which lactic acidosis was the presenting feature of a previously undiagnosed case of metastatic breast cancer in a pregnant woman and that resolved with successful antineoplastic treatment. The authors review the likely cause and management of the condition.     

Lactic acidosis and colon cancer: oncologic emergency?

We report the case of a 44-year-old woman who presented shortly after the diagnosis of metastatic colon cancer with profound lactic acidosis in the absence of tissue hypoperfusion or hypoxemia. Her acid-base disturbance was unresponsive to medical management but resolved after initiation of systemic chemotherapy. In addition to malignancy associated lactic acidosis, this case illustrates several other issues, including factors involved in choosing the initial chemotherapy regimen and sequencing subsequent therapies, and the role of carcinoembryonic antigen (CEA) in following response to treatment. It is important to report this case of a rare but serious complication of malignancy in order to increase recognition and understanding of this presentation.     

A typical presentation of acute myeloid leukemia

A young man who presented with fever, altered sensorium and sudden onset tachypnea, is described. Arterial blood gas analysis, revealed the presence of severe high anion gap metabolic acidosis, with compensatory respiratory alkalosis and normal oxygen saturation. A detailed neurological, nephrological, biochemical and hematological evaluation, revealed the presence of Acute myeloid leukemia, with lactic acidosis and hyponatremia. There are very few reports of presentation of leukemia as lactic acidosis. This case report highlights the need for emergency room physicians, to consider the possibility of lactic acidosis, as one of the causes of high anion gap acidosis and to meticulously investigate the cause of lactic acidosis. We describe a rare clinical instance of lactic acidosis as the presenting manifestation of Acute myeloid leukemia.     

Small cell lung cancer accompanied by lactic acidosis and syndrome of inappropriate secretion of antidiuretic hormone

Lactic acidosis is a rare complication in lung cancer. We report a case of lung cancer accompanied by both syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and lactic acidosis. A 70-year-old man was referred to our hospital for examination of a left hilar mass shadow on a chest X-ray film. Small cell lung cancer (SCLC) was demonstrated by brushing the bronchial mucosa of the left lower lobe bronchus. His laboratory data showed SIADH and lactic acidosis that were probably due to SCLC. Fluid restriction improved SIADH, and combination chemotherapy for SCLC improved the lactic acidosis although the tumor size did not change.     

Breast cancer in brothers: case reports and a review of 30 cases of male breast cancer.

Two brothers with breast cancer are presented. One died 8 years after diagnosis and the other is presently living at 1 year with metastatic disease. The courses of 28 other previously unreported male patients with carcinoma of the breast are reviewed, and the possibility of male breast carcinoma being metastatic disease from the prostate is discussed. Useful etiologic information might be obtained from following the offspring of male breast cancer patients to see if they are at increased risk of developing the disease.     

Breast carcinoma metastatic to the bladder and renal pelvis requiring fulguration

Breast cancer metastatic to the bladder has rarely been reported in the literature. A patient presented to our institution with pathologically confirmed breast cancer metastatic to the bladder with renal pelvis involvement as seen on retrograde pyelography. We believe cystoscopy with biopsy and fulguration to be the treatment of choice for breast cancer that has metastasized to the bladder because of the low rate of survival in patients with hematuria related to metastatic breast cancer.     

Extracellular acidification alters lysosomal trafficking in human breast cancer cells

Cancer cells invade by secreting degradative enzymes, which are sequestered in lysosomal vesicles. In this study, the impact of an acidic extracellular environment on lysosome size, number, and distance from the nucleus in human mammary epithelial cells (HMECs) and breast cancer cells of different degrees of malignancy was characterized because the physiological microenvironment of tumors is frequently characterized by extracellular acidity. An acidic extracellular pH (pH(e)) resulted in a distinct shift of lysosomes from the perinuclear region to the cell periphery irrespective of the HMECs' degree of malignancy. With decreasing pH, larger lysosomal vesicles were observed more frequently in highly metastatic breast cancer cells, whereas smaller lysosomes were observed in poorly metastatic breast cancer cells and HMECs. The number of lysosomes decreased with acidic pH values. The displacement of lysosomes to the cell periphery driven by extracellular acidosis may facilitate exocytosis of these lysosomes and increase secretion of degradative enzymes. Filopodia formations, which were observed more frequently in highly metastatic breast cancer cells maintained at acidic pH(e), may also contribute to invasion.     

Metastatic breast carcinoma presenting as persistent diarrhea.

Patients with breast carcinoma metastatic to the colon generally present with multiple symptoms, usually pain, vomiting, nausea, and ascites. We describe a patient who presented only with persistent diarrhea, underwent surgery for colon cancer, and, on pathological evaluation of the surgical specimen, was found to have metastatic breast cancer affecting the colon. Metastatic breast cancer should therefore be suspected in patients with a history of breast cancer and diarrhea of unknown cause that is not accompanied by other symptoms. Evaluating such patients by colonoscopy and biopsy would provide important information relevant to choosing between colon surgery and systemic therapy.     

Carboplatin in combination therapy for metastatic breast cancer

BACKGROUND: Anthracycline-based regimens have a limited role in patients with metastatic breast cancer due to cumulative cardiotoxicity and their common use in adjuvant chemotherapy. New nonanthracycline regimens are, therefore, needed for metastatic disease. Single-agent carboplatin is active in patients with previously untreated metastatic breast cancer, producing response rates of 20%-35%. Preclinical studies have demonstrated synergistic antitumor efficacy of carboplatin and trastuzumab in HER2(+) models. METHODS: Phase II and III clinical trial data of combination therapy with carboplatin (Paraplatin; Bristol-Myers Squibb; Princeton, NJ), a taxane, and/or trastuzumab (Herceptin; Genentech, Inc.; South San Francisco, CA) in metastatic breast cancer were identified from multiple sources, including: A) clinical trial data published in peer-reviewed journals within the last 5 years; B) preliminary clinical trial data from abstracts recently presented at national meetings; and C) phase III protocols currently evaluating carboplatin-based combination regimens. RESULTS: In several phase II studies, combination carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb) therapy was active and reasonably well tolerated in the first-line treatment of metastatic breast cancer, producing objective response rates of 53%-62%-substantially higher rates than those seen in other phase II trials of either drug alone. Similar phase II data for carboplatin with docetaxel (Taxotere; Aventis; Bridgewater, NJ) have been reported, and recent phase III data suggest that adding carboplatin to a paclitaxel/trastuzumab regimen produces superior efficacy than paclitaxel/trastuzumab alone for patients with HER2(+) metastatic disease. Drug scheduling plays an important role in the therapeutic ratio of this combination treatment. CONCLUSIONS: Incorporation of carboplatin as a standard agent in first-line treatment of metastatic breast cancer has support from several recent studies. Preliminary results of combination carboplatin/taxane therapy with trastuzumab in metastatic disease are encouraging, and other carboplatin combinations are also being investigated in other phase II and III trials in patients selected based on the HER2 status of their cancer. Results are eagerly awaited.     

Primary breast tumor levels of suspected molecular determinants of cellular sensitivity to cyclophosphamide, ifosfamide, and certain other anticancer agents as predictors of paired metastatic tumor levels of these determinants

PURPOSE: Cyclophosphamide is one of the most frequently used agents in the neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast cancers. Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular content of two aldehyde dehydrogenases, viz ALDH1A1 and ALDH3A1, and glutathione. Breast tumor levels of these "determinants of cellular sensitivity to the oxazaphosphorines" are known to vary widely, and the decision as to whether or not to use an oxazaphosphorine as part of the therapeutic strategy to treat breast cancer in any given patient is likely to depend, in large part, on the levels of these determinants in that cancer. ALDH1A1, ALDH3A1, and glutathione levels can be easily quantified in primary breast tumors and in detectable metastatic breast tumors present in axillary lymph nodes because the amounts of tissue required for the desired analysis can be readily obtained, whereas these levels cannot be quantified in residual metastatic breast cancer cell populations, i.e., those that escape detection and/or that are inaccessible to surgical harvest. The inability to directly quantify residual metastatic breast cancer cell ALDH1A1, ALDH3A1, and glutathione levels would not preclude a rational decision with regard to the inclusion/exclusion of an oxazaphosphorine as part of the chemotherapeutic strategy intended to eradicate residual metastatic breast cancer cells if primary breast tumor levels of these determinants reliably predicted those in metastatic breast cancer cells. METHODS: ELISAs and spectrophotometric assays were used to quantify enzyme and glutathione levels in paired human primary and locally advanced metastatic breast tumor samples. RESULTS: Primary breast tumor ALDH1A1 and ALDH3A1 levels were highly predictive of their respective levels in paired metastatic breast tumors present in axillary lymph nodes (r2 = 0.80 and 0.85, respectively). On the other hand, those of glutathione were relatively poorly predictive of its levels in paired metastatic offshoots (r2 = 0.35). Primary breast tumor levels of some additional enzymes known to catalyze the detoxification/toxification of various anticancer agents, though not of cyclophosphamide, were poorly predictive (DT-diaphorase and glutathione S-transferases alpha, mu, and pi) or not predictive (cytochrome P450 1A1) of their respective levels in paired metastatic offshoots. CONCLUSION: Since ALDH1A1, ALDH3A1 and, to a lesser extent, glutathione levels in primary breast tumors reliably predicted those in detectable and easily accessible metastatic breast cancer cell populations, viz those in axillary lymph nodes, they are also likely to be predictive of these levels in undetectable and/or relatively inaccessible metastatic breast cancer cell populations. Thus, quantification of primary breast tumor ALDH1A1, ALDH3A1 and, to a lesser extent, glutathione levels prior to the initiation of not only neoadjuvant but also adjuvant and high-dose breast cancer chemotherapy is likely to be of value in the rational design of individualized chemotherapeutic regimens intended to eradicate breast cancer cells with a minimum of untoward effects.     

The role of capecitabine in first-line treatment for patients with metastatic breast cancer

Capecitabine is an important drug in the therapeutic armamentarium for metastatic breast cancer. A comprehensive worldwide clinical trial program involving >10,000 patients with locally advanced and metastatic breast cancer has provided evidence for the current treatment strategies. On the basis of data demonstrating consistent activity across several trials in patients with heavily pretreated breast cancer, capecitabine was approved in the U.S. in 1998 for the treatment of patients with metastatic disease resistant to paclitaxel and anthracycline-containing therapy, with later European Union approval for single-agent capecitabine in the metastatic setting. Capecitabine plus docetaxel (XT) was approved by the U.S. Food and Drug Administration for the treatment of metastatic breast cancer in 2001 on the basis of the large phase III trial comparing XT with docetaxel alone, which showed a survival advantage for combination therapy compared with single-agent therapy. This was shortly followed by European approval for the combination in metastatic breast cancer. The clinical utility of capecitabine in the management of breast cancer is supported by its convenient oral dosing schedule and favorable safety profile, as well as its excellent clinical activity in primary and metastatic breast cancer. Recently, clinical trials have studied single-agent capecitabine as first-line treatment and evaluated other capecitabine-containing combinations with cytotoxic and novel targeted agents.     

Multiple myeloma associated with lactic acidosis

Type B lactic acidosis is rare among patients with malignant diseases. To date only one case report has documented lactic acidosis occurring in a patient with multiple myeloma (MM). Our patient, a 55-year-old black man, was diagnosed with stage IIIA immunoglobulin G-kappa (IgG-kappa) MM in September 1995. He was found to have severe lactic acidosis at the time of second relapse. During the terminal phase of his disease, he required multiple hospitalizations for management of lactic acidosis and other complications of his MM. No other cause of his elevated lactate levels was identified. Although type B lactic acidosis may more commonly occur in patients with leukemia or lymphoma, it may rarely present in patients with rapidly progressive and refractory MM.     

Metastatic lobular carcinoma of the breast to the vulva: a case report and review of the literature

Primary breast-like vulva cancer, as well as metastatic disease of breast cancer to the vulva are described to be very rare, especially many years after the treatment of the primary breast tumor. Breast cancer rarely metastasizes to the vulva without finding other metastatic sites. We report a case of a 93-year-old woman with an isolated metastatic vulvar nodule thirteen years after the surgical treatment of primary breast cancer. The prior histology was a node negative invasive lobular breast cancer. The histology of the vulvar nodule was similar to the primary breast cancer. No other metastatic sites were found by both clinical examination and imaging. When isolated metastasis to the vulva is found, a primary cancer in the gynaecological area should be excluded first. KEY WORDS: Breast cancer - Vulvar metastasis - Rare breast metastasis.     

Iatrogenic lactic acidosis: association with hypertonic glucose administration in a patient with cancer

A case of lactic acidosis associated with the administration of hypertonic glucose to a patient with a bulky undifferentiated carcinoma is presented. Characteristic alterations in amino acid concentrations were observed during the period of lactic acidosis. Resolution of the metabolic abnormalities were seen with discontinuation of glucose infusion. Short-term glucose infusion in a 90 minute iv glucose tolerance test resulted in an increase in serum lactate and appropriate changes in serine, ornithine, taurine, alanine, and arginine despite normal hormonal responsiveness.     

Weekly administration of docetaxel and paclitaxel in metastatic or advanced breast cancer

The taxanes docetaxel (Taxotere; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com) and paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) have significant clinical activity in metastatic breast cancer. A number of clinical trials have evaluated the tolerability and efficacy of weekly taxane administration to optimize the benefit-to-risk ratio in metastatic breast cancer. Single-agent studies with docetaxel and paclitaxel in metastatic breast cancer show clinically significant antitumor activity even in advanced, heavily pretreated, resistant, and/or refractory disease. This activity is also evident with taxane-based combination regimens. Severe hematologic and nonhematologic toxicities are infrequent, with other toxicities noted based on the dose and weekly regimen selected. Weekly docetaxel and paclitaxel regimens represent valuable therapeutic options for women with metastatic breast cancer and have entered evaluation as part of adjuvant therapy for this disease.     

生长抑素受体在复发和转移性乳腺癌组织中的表达及意义

目的 探讨生长抑素受体(SSTR)在复发和转移性乳腺癌组织中的表达及意义.方法 采用免疫组化法检测86例复发和转移性乳腺癌切除转移病灶、转移灶旁组织和正常组织中的SSTR,比较分析3组表达情况;同时将检测结果与这86例患者第1次术后的SSTR表达情况进行比较.结果 局部复发癌组织、转移淋巴结组织中SSTR的阳性表达率分...     

Reduced thoracic vertebrae metastases following post mastectomy parasternal irradiation

A retrospective study of 118 women with breast cancer metastatic to bone is presented. All had originally received post mastectomy adjuvant radiation therapy for Stage II (T2 N0, T2 N1, T1 N1) infiltrating duct carcinoma of breast. Sixty-two women (group A) received a parasternal portal and 56 women (group B) did not. There was significantly less metastatic involvement of the mid-dorsal vertebrae D5-6-7-8, 13% in group A compared to 60% in group B. The mean time to diagnosis of metastatic disease was 33 months (group A) and 36 months (group B). The dose of radiation to the vertebrae through which the parasternal beam exited was estimated at between 1000-1600 rad over three to four weeks. This observation may have significant implications for the management of high risk operable breast cancer.     

Can Women With HER2-Positive Metastatic Breast Cancer Be Cured?

Breast cancer that is characterized by amplification or over expression of human epidermal growth factor receptor 2 (HER2) accounts for 15% to 20% of all forms of the disease. Although HER2 amplification has been associated with aggressive disease behavior and poor prognosis, the development and availability of a number of HER2-targeted agents has led to improved outcomes for patients with HER2-positive metastatic breast cancer, with data suggesting that overall survival has substantially improved in the past 2 decades. An increasing proportion of HER2-positive metastatic breast cancer is diagnosed as de novo stage IV disease. Patients with de novo metastases are traditionally classified in the general category of metastatic breast cancer and not analyzed as a distinct subgroup, though response to therapy and disease outcomes may differ from that of disease that recurred after early stage disease. Among patients with HER2+ de novo metastatic breast cancer, those who achieve a complete response have a prolonged progression‐free survival and overall survival. Moreover, the fact that some patients achieve a prolonged durable response has raised interest and renewed discussion about whether cure is feasible in the complex context of metastatic breast cancer. In this review, available data associated with the possibility of cure in the population of patients with HER2+ de novo metastatic breast cancer are presented and discussed in detail.     

国产多西他赛为主的联合化疗治疗转移性乳腺癌

 目的 观察国产多西他赛为主的联合化疗治疗转移性乳腺癌的疗效、毒副反应和临床受益反应（Clinical　benefit　response，CBR），并以进口多西他赛作对照。方法 A组30例转移性乳腺癌患者，既往未采用蒽环类药物治疗的14例采用国产多西他赛联合阿霉素治疗（A1组），既往蒽环类药物治疗失败的16例采用国产多西他赛联合卡培他滨治疗（A2组）；B组25例转移性乳腺癌患者作对照，其中未采用蒽环类药物治疗的11例采用进口多西他赛联合阿霉素治疗（BI组），既往蒽环类药物治疗失败的14例采用进口多西他赛联合卡培他滨治疗（B2组）；3周为1个周期，2周期评价疗效，记录毒副反应。结果 A组有效率（CR＋PR）66．7％，肿瘤控制率（CR＋PR＋SD）93．3％。毒副反应主要为骨髓抑制和脱发，可耐受，无治疗相关性死亡。CBR评价有效者73．3％；B组有效率68％，肿瘤控制率92％。毒副反应与A组相似。CBR评价有效者72％。结论 国产多西他赛为主的联合化疗治疗转移性乳腺癌有较好的疗效，毒副反应可耐受，临床受益反应良好，与进口多西他赛的疗效和不良反应相似。