Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells.

In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα) positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis.

[Padma 28 in cytostatic-induced dysesthesia and edema of the hands--a case from practice]. / Padma 28 bei Zytostatika-induzierten Dysästhesien und Ödemen der Hände--ein Fall aus der Praxis.

BACKGROUND: The herbal complex formula Padma 28 is mostly used in circulation-induced paresthesia, in feelings of heaviness and tension in the legs and arms, and in numbness of the hands and feet. CASE REPORT: In the case presented here of a patient with breast cancer, status after full mastectomy, severe cytostatic-induced edema, and dysesthesia occurred on both hands, which made simple, daily tasks impossible. Treatment with high doses of vitamin B6 was unsuccessful. Padma 28 was given under the rationale to improve the microcirculation and thus to protect the delicate nerve endings. Despite ongoing chemotherapy, this treatment led to an improvement of the dysesthesia after 2 weeks, and after 5 weeks, the sensory disturbances and edema of the hands had completely disappeared. CONCLUSION: Padma 28 seems therefore suitable for adjuvant use in paresthesia and swelling caused by cytotoxic drugs during chemotherapy.

Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study.

BACKGROUND: Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. PATIENTS AND METHODS: Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. RESULTS: Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. CONCLUSION: IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.

Treatment decision making among Chinese women with DCIS.

One result of the widespread screening mammography is a 200% increase in the rates of breast ductal carcinoma in situ (DCIS). Treatment decision making among Chinese women diagnosed with DCIS remains understudied. This study examined Chinese-Canadian women's experiences (N = 26): (1) with treatment decision making (mastectomy or breast conserving surgery) and (2) their reflections on the decision-making process. Interviews in Cantonese, Mandarin, or English were transcribed and translated, and a content analysis conducted. Women's treatment decisions reflected a lack of understanding of DCIS, the desire to rid themselves of breast cancer forever, and the influence of significant others. English as a second language and use of medical jargon impeded their ability to make informed treatment decisions. Women's reflections on the decision-making process provided insights into how to improve information and support treatment decision making in ways that are accessible to them.

Neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with systemic chemotherapy in patients with breast cancer.

BACKGROUND AND PURPOSE: This is the first study investigating neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with chemotherapy in patients with breast cancer. The goal was to evaluate the type of surgical treatment, histopathologic response, side effects, local control, and survival. PATIENTS AND METHODS: 53 patients, who could not be treated with breast-conserving surgery due to initial tumor size (36/53) or due to an unfavorable breast-tumor ratio (17/53), were analyzed retrospectively. All but one were in an intermediate/high-risk group (St. Gallen criteria). The patients received a neoadjuvant protocol consisting of systemic chemotherapy combined with fractionated HDR brachytherapy (2 x 5 Gy/day, total dose 30 Gy). In cases, where breast-conserving surgery was performed, patients received additional external-beam radiotherapy (EBRT, 1.8 Gy/day, total dose 50.4 Gy). In patients, who underwent mastectomy but showed an initial tumor size of T3/T4 and/or more than three infiltrated lymph nodes, EBRT was also performed. RESULTS: In 30/53 patients (56.6%) breast-conserving surgery could be performed. The overall histopathologic response rate was 96.2% with a complete remission in 28.3% of patients. 49/53 patients were evaluable for follow-up. After a median of 58 months (45-72 months), one patient showed a mild fibrosis of the breast tissue, three patients had mild to moderate lymphatic edema of the arm. 6/49 (12.2%) patients died of distant metastases, 4/49 (8.2%) were alive with disease, and 39/49 (79.6%) were free from disease. Local recurrence was observed in only one case (2%) 40 months after primary therapy. After mastectomy, this patient is currently free from disease. CONCLUSION: The combination of interstitial HDR brachytherapy and chemotherapy is a well-tolerated and effective neoadjuvant treatment in patients with breast cancer. Compared to EBRT, treatment time is short. Postoperative EBRT of the whole breast -- if necessary -- is still possible after neoadjuvant brachytherapy. Even though the number of patients does not permit definite conclusions, the results are promising regarding survival and the very low rate of local recurrences.

Raloxifene rebound regression.

The first case of clinical remission of metastatic breast after the withdrawal of raloxifene is reported. A postmenopausal woman was treated for stage II breast cancer with a modified radical mastectomy and adjuvant cyclophosphamide, doxorubicin, and 5-flurouracil followed by tamoxifen for 5 years. One year following the cessation of tamoxifen, osteopenia was noted and raloxifene was begun. Two years following the start of raloxifene, supraclavicular adenopathy and lung metastases developed, which regressed after discontinuation of raloxifene. Although raloxifene is not frequently given to women with previous breast cancer, increasing use in osteopenic women may lead to cancer developing in these raloxifene-treated women; this despite the major reduction in the incidence of breast cancer in raloxifene-treated versus placebo-treated women. A clinically significant response to the withdrawal of a hormone, used either for the treatment of breast cancer or for some other reason, is not a rare event, and the therapeutic usefulness of observation only for a rebound regression is a frequently overlooked strategy in the treatment of breast cancer.

1-hexylcarbamoyl-5-fluorouracil + cyclophosphamide + tamoxifen versus CMF + tamoxifen in women with lymph node-positive breast cancer after primary surgery: a randomized controlled trial.

We studied the usefulness of the oral 5-FU anti-cancer drug 1-hexylcarbamoyl-5-fluorouracil (HCFU) + cyclophosphamide (CPM) + tamoxifen (TAM) (HCT group) in comparison with CMF + TAM (CMFT group) in adjuvant therapy for breast cancer by a non-inferiority study based on a multi-institutional joint study. Clinical stage I, II primary breast cancers with histologically positive axillary lymph node metastasis were randomly assigned to the HCT group or the CMFT group after primary surgery. We registered 136 cases (HCT group 68 cases, CMFT group 68 cases). No significant difference in the 5-year overall survival rate (OS) and the 5-year disease-free survival rate (DFS) was found between the two groups. In the stratified analysis, DFS in cases in which the number of metastatic lymph nodes was 1-3 was significantly better in the HCT group (HCT group 84.3%, CMFT group 69.4%, log-rank test p=0.0496). No significant difference in the total incidence of adverse effects was found between the two groups, but there were significantly less adverse effects of grade 2 or over in the HCT group (p=0.034). The QOL survey at 3 months after surgery showed a significant decline of the QOL regarding lassitude, degree of difficulty in daily life, satisfaction with treatment and present mood in the CMFT group. Study results suggest that 2-year HCT therapy including the oral 5-FU anti-cancer drug HCFU is a useful adjuvant therapy which can replace CMFT therapy in early breast cancer cases with 3 or lower metastatic lymph nodes.