Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast

BACKGROUND: Few women with locally advanced breast cancer remain disease-free, even for 2 years. Response to induction chemotherapy may be associated with longer disease-free and overall survival rates. The role of breast conservation in selected patients with response to induction chemotherapy was evaluated. METHODS: Since 1979, patients with Stages IIB and III breast cancer have undergone induction chemotherapy; patients with response continued chemotherapy until a plateau of regression was achieved. Before 1983, all patients having a response to chemotherapy underwent mastectomy; since 1983, selected patients have undergone breast conservation. Outcomes were tallied comparing these two groups of patients. RESULTS: The study group included 189 women, who were followed up for 12-159 months (median, 46 months) after diagnosis. Of the patients, 85% had a response to induction chemotherapy. Patients with no response were excluded from additional consideration in this study. One hundred three (64%) women underwent mastectomy; 55 (36%) were treated with breast conservation. The disease-free 5-year survival rate was 61% for all patients with a response to chemotherapy; 56% for those having mastectomy and 77% for those having breast conservation. The overall 5-year survival rate was 69% for all patients with a response to chemotherapy, 67% for those undergoing mastectomy and 80% for those having breast conservation. CONCLUSIONS: Induction chemotherapy achieves significant tumor regression in most women with locally advanced breast cancer, permitting subsequent breast conservation or mastectomy with a greater expectation of long-term success. Breast conservation is used more frequently with the same expectation of success as mastectomy, presuming careful selection based on response to chemotherapy.     

Bendamustine as salvage treatment in patients with advanced progressive breast cancer: a phase II study

A phase II pilot study of bendamustine as salvage treatment in patients with advanced breast cancer was performed to determine the objective response rates and make further observations on the toxicity of this drug. A group of 37 patients, pretreated with chemotherapy for advanced disease, entered the trial. Treatment consisted of 150 mg/m2 bendamustine on days 1 and 2 of a 4-week treatment course. Patients continued to receive treatment until complete remission and then two further courses, until tumour progression or unacceptable toxicity ensued. A total of 36 patients received at least one treatment course and were assessable for toxicity; 33 patients were evaluable for treatment results. Dose-limiting grade 3 and 4 WHO toxicity occurred in 5 and 3 patients respectively; 27% of patients entered complete or partial tumour remission. The median time to tumour progression was 2 months with a range of 1-14 months. The efficacy of bendamustine was apparently independent of pretreatment with anthracyclines, suggesting a lack of cross-resistance between bendamustine and anthracyclines. It can be concluded that bendamustine in the dose and application schedule used here is active in the salvage therapy of women with advanced breast cancer. The toxicity was acceptable. Future studies have to confirm the data of this pilot trial and to define the role of bendamustine in the combination chemotherapy of metastatic breast cancer that has been suggested by previous trials.     

Studies with high-dose chemotherapy and subsequent autologous stem cell transplantation in breast carcinoma

Survival rates for several subgroups of patients with breast cancer treated with conventional therapy remain poor. Only about 30% of patients with primary breast cancer involving more than 9 axillary lymph nodes remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy and radiotherapy. Metastatic breast cancer with 5 year survival rates of about 3% generally represents incurable disease. Chemotherapeutic agents are conventionally limited by side effects. The easy procurement of haematopoietic stem cell support through mobilization of peripheral blood progenitors has spurred the development of new strategies employing high-dose treatment for treatment of high risk breast cancer. Autologous stem cell support antagonizes chemotherapy-induced myelotoxicity and thereby allows dose escalation by a factor of 1.5 to about 20. Pilot studies evaluating significant dose escalation in adjuvant treatment of patients with advanced disease have resulted in an apparent improvement in event-free survival rates to over 70%. Repetitive applications of chemotherapy at myeloablative doses are now increasingly being used. Data from prospectively randomized phase III trials will not be available before the end of 1998. For metastatic breast cancer one prospective, randomized clinical trial has been published. Results are significantly better for patients who have been treated by high-dose chemotherapy compared to patients who received conventional polychemotherapy (median survival 90 vs. 45 weeks). For methodological reasons (small patient numbers, patient selection, weak standard therapy etc.) results from the trials cited above are under discussion. Until publication of further results from ongoing phase III trials HDC for breast cancer remains experimental and should not be given outside of clinical trials.     

Palliative therapy in advanced ovarian cancer: balancing patient expectations, quality of life and cost

The goals of chemotherapy for recurrent/refractory ovarian cancer are the palliation of disease-related symptoms, and improvement of quality and quantity of life. Previous studies of palliative therapy in advanced ovarian cancer have focused on surrogate measures of patient benefit rather than evaluating palliative end-points such as quality of life and clinical benefit. The impact of palliative chemotherapy on survival, quality of life and cost in advanced ovarian cancer are unknown as there have been no studies comparing palliative treatment with best supportive care. Although there is insufficient information from existing studies to determine whether palliative therapy in advanced ovarian cancer is cost-effective, there is some evidence to suggest that chemotherapy has a role in palliation of symptoms with an apparent improvement in quality of life. We relate the results of two studies. (i) A prospective study evaluating the cost of second/third-line chemotherapy as well as its effectiveness, which found the mean total cost per patient for the study period (one line of chemotherapy) was Canadian $12500. In addition, half of patients seemed to derive some palliative benefit and a quarter of patients had an objective response in their disease. (ii) A retrospective study evaluating all costs from the initiation of palliative chemotherapy until death which demonstrated a cost of Canadian $53000 per patient. Our studies demonstrate that patient expectations of palliative therapy in ovarian cancer are high and patients are willing to put up with significant toxicity for modest benefit. Although palliative therapy may be associated with high costs, even modest prolongation of survival can render such treatment cost-effective. The major cost saving associated with palliative therapy is from the reduced need for hospitalization towards the end of life. Future studies in recurrent/refractory ovarian cancer should focus on palliative end-points and include a comparison with best supportive care.     

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.     

Systemic therapy for breast cancer

Currently available information suggests that the optimal duration of adjuvant therapy for breast cancer patients with no involved axillary nodes is 5 years, though controversy about this recommendation persists. In postmenopausal patients, disease-free survival appears to be improved by the addition of combination chemotherapy to tamoxifen. Recently reported studies indicate that there is no benefit to dose escalation of cyclophosphamide in adjuvant therapy and that the risk of secondary leukemia may be increased. The combination of paclitaxel and doxorubicin has been reported in single-institution studies to produce high response rates but may also be cardiotoxic. Recent reports indicate that a pharmacokinetic interaction between these two drugs may cause these clinical findings. New agents that may be of utility in the management of advanced or primary breast cancer include novel hormonal agents, notably the aromatase inhibitors, and the bisphosphonates.     

Cell fate and morphogenetic movement in the late mouse primitive streak

Metastatic breast cancer remains incurable by conventional means and is the second leading cause of all cancer deaths in women in the United States. Laboratory and clinical studies have shown chemotherapy dose intensity may be important in breast cancer therapy, and therefore clinical trials have been investigating high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) for the past decade. Initial Phase I trials in heavily pretreated patients demonstrated good response rates but short survival times. The next generation of trials used HDC as initial treatment for metastatic breast cancer and showed improved results. Most recently, patients receive HDC after "induction" chemotherapy to minimize tumor burden prior to HDC. Results from these most recent trials are encouraging, with complete remissions (CR) achievable in at least half of patients and long-term survivors noted. An ongoing randomized trial of HDC versus conventional chemotherapy should answer whether HDC is superior to conventional chemotherapy for metastatic breast cancer. Based on encouraging data from a preliminary trial, two ongoing randomized trials are comparing HDC versus conventional chemotherapy in high-risk primary breast cancer. Technological improvements, better supportive care and experience have all contributed to decrease the morbidity and mortality of this procedure. Additionally, hospitalizations have become shorter and costs may be decreasing. This review will discuss the issues pertinent to this modality in the past and present, including chemotherapy regimens, stem cell technology and related issues, outcomes, ongoing trials and future directions for consideration.     

Pattern of failure in patients with inflammatory breast cancer treated by alternating radiotherapy and chemotherapy

BACKGROUND: Patients with inflammatory breast cancer have a high risk of developing a local recurrence and/or distant metastases. Treatment with combined chemotherapy and locoregional radiotherapy contributes to a decrease in both risks. This study presents treatment results and evaluates the pattern of failure when an alternating chemoradiotherapy schedule is used. METHODS: One hundred twenty-five patients with nonmetastatic inflammatory breast cancer were treated with an alternating schedule of radiotherapy and chemotherapy. All women recruited were younger than 70 years of age and had a T4d, histologically proven infiltrating carcinoma with N0 to N2 axillary disease. The protocol consisted of three cycles of induction chemotherapy with doxorubicin, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil followed by three series of locoregional radiotherapy, delivering a total dose of 65-75 Gy to the breast tumor. Five additional cycles of chemotherapy with 5-fluorouracil/doxorubicin/cyclophosphamide were to be administered in between the first two and after the third radiotherapy course. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. RESULTS: Toxicity was moderate and this strategy proved feasible although most of the patients only received six instead of the eight planned cycles of chemotherapy. Eighty-two percent of the patients achieved a complete response at the end of the treatment. The cumulative 5-year local failure and distant metastasis rates were 27% and 53%, respectively. Assuming competing events, local failures, contralateral recurrences, and distant metastases were the first site of failure in 18%, 5%, and 38% of patients, respectively. The 5-year overall and disease free survival rates were 50% and 38%, respectively. The main prognostic factor was tumor size. CONCLUSIONS: Alternating high doses of radiotherapy and chemotherapy is a feasible treatment schedule and permits breast conservation. Disease free survival is comparable to that of recently published series. As the main causes of failure are distant metastases, higher dose chemotherapy should be evaluated, in an attempt to further improve overall survival.     

GABAergic stimulation regulates the phenotype of hippocampal interneurons through the regulation of brain-derived neurotrophic factor

PURPOSE: Information concerning the differences between older and younger women with breast cancer, treated with standard therapy, is lacking from many prospective series. The purpose of this study is to identify factors that influence treatment decisions and determine if women age 65 and older are treated differently than younger women. The outcomes of older women would then be compared to younger to determine if treatment differences influence outcome. METHODS AND MATERIALS: The records of 558 women with early invasive breast cancer who were treated with breast conserving surgery and radiation therapy were retrospectively reviewed. Four hundred thirty-two women under the age of 65 (range: 24-64) and 126 women age 65 and older (range: 65-85) were assessed for treatment differences including breast reexcision, extent of axillary dissection, extent of breast and nodal irradiation, and the use of chemotherapy or hormonal therapy. Differences in the treatment of the two groups were determined and the end points of local control, disease-free survival, and overall survival were compared. Median follow-up was 5.5 years. RESULTS: The two treatment groups had identical pathologic TNM staging with the exception that 21% of the older age group and 5% of the younger group did not undergo axillary dissection. Women age 65 and older were less likely to have a reexcision, extensive axillary dissection, chemotherapy, or nodal irradiation. They were more likely to receive hormonal therapy. Reexcision in older women was positively influenced by a family history of breast cancer and negatively influenced by a history of previous malignancy. None of the patients who were treated without and axillary dissection suffered a regional recurrence. Although local control was better in older patients, there were no differences in disease-free or overall survival for the two groups. DISCUSSION: The findings of this study reveal that older patients have significant treatment differences as compared to younger patients; however, despite these differences, similar local control and survival were achieved at 5 to 10 years. With the expected survival of older women increasing, the prospective evaluation of treatment options for older women should be considered.     

Outpatient chemotherapy of advanced breast cancer in a community setting: a five-drug regimen

Forty-two (37 evaluable) unselected women with advanced breast carcinoma were treated with a modified "Cooper regimen" in a community setting. After 12 weeks of induction therapy, the patients were evaluated for response and toxicity. The 74% overall response rate (78% in the evaluable group) compares favorably with that of other series. The median duration of remission was 13.7 months. The median survival was 17 months for the evaluable patients and 14 months for the entire group. Twenty-two percent of the patients required hospitalization during the induction phase, and 35% were treated exclusively as outpatients during all phases of therapy. There was only one drug-related death. It is concluded that a complex chemotherapeutic regimen can be managed adequately by physicians experienced in chemotherapy in a community setting with results comparable to those from cancer centers.     

Do patients with advanced breast cancer benefit from chemotherapy?

This study aimed to assess the proportion of patients with advanced breast cancer who report benefit from first-line palliative chemotherapy using a simple global measure of wellbeing and to identify factors predicting benefit. A consecutive series of women with advanced breast cancer undergoing first-line palliative chemotherapy was evaluated. The main outcome measure was patient report of overall wellbeing assessed at post-treatment interview. Physical, psychological and functional status were assessed using the Rotterdam Symptom Checklist (RSCL) on three occasions (pretreatment, at the start of the third cycle and post treatment). It was planned that treatment would be discontinued after six cycles (i.e. 18-24 weeks). One hundred and sixty patients started treatment, of whom 155 were assessable for quality of life. After treatment, 41 (26%) patients reported they felt better, 29 (19%) felt the same and 34 (22%) felt worse than they did before treatment. The other 51 (33%) patients either died or stopped attending the hospital before the post-treatment interview and were assigned as treatment 'failures'. Patients who reported feeling better after treatment had improvements in psychological distress (P < 0.0001), pain (P = 0.01), lack of energy (P = 0.02) and tiredness (P = 0.02), as well as improvement in functional status (P = 0.07). Feeling better was also correlated with disease response (P = 0.03). Feeling worse after treatment or treatment 'failure' was predicted by the pretreatment presence of a dry mouth (P = 0.003) and high levels of psychological distress (P = 0.03). Pretreatment lack of energy (P = 0.01), dry mouth (P = 0.02), presence of liver metastases (P = 0.03) and breathlessness (P = 0.03) predicted treatment 'failures'. The results of this study suggest that first-line palliative chemotherapy for advanced breast cancer confers benefit on a substantial proportion of patients, with about one-quarter feeling better after treatment and nearly a half feeling better or the same some 4-6 months after the start of treatment. Factors identified in this study may assist clinicians in deciding which patients should not be offered treatment, because of high risk of feeling worse or treatment 'failure'. This work now needs to be validated on a further cohort of women receiving chemotherapy for advanced breast cancer.     

Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer

PURPOSE: To evaluate the safety and efficacy of breast-conserving therapy for young women with a family history (FH) suggestive of inherited breast cancer susceptibility. MATERIALS AND METHODS: A total of 201 patients aged 36 or younger at diagnosis treated with breast-conserving surgery and radiation therapy (> or = 60 Gy) for early-stage breast cancer were categorized by FH. FH was considered positive in 29 patients who, at the time of diagnosis, had a mother or sister previously diagnosed with breast cancer before age 50 or ovarian cancer at any age. Clinical, pathologic, and demographic variables; sites of first failure; disease-free survival; and overall survival (OS) were compared between FH-positive and -negative groups. Median follow-up time was 11 years. RESULTS: Patient and tumor features were similar between those with and without an FH. Regression analysis of sites of first failure at 5 years demonstrated a risk ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of local, regional, and distant failure and disease-free survival or OS did not differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi heritage were not significantly predictors of patterns of failure. CONCLUSION: Breast-conserving surgery combined with radiation therapy is not associated with a higher rate of local recurrence, distant failure, or second (non-breast) cancers in young women with an FH suggestive of inherited breast cancer susceptibility compared with young women without an FH. However, their increased risk of opposite breast cancer should be taken into account when considering breast conservation as a treatment option.     

Schwannoma with sweat duct differentiation

In a randomized trial of second line hormone therapy 56 postmenopausal women with advanced breast cancer received low dose aminoglutethimide (AGT) 125 mg twice daily without hydrocortisone (27 patients), or hydrocortisone (HC) 20 mg twice daily (29 patients). The two groups were well-matched for previous response to tamoxifen (TAM) therapy (AGT (35%) vs HC (32%)) and for relapse on adjuvant TAM. The mean age of the two groups was 69.2 years (AGT) and 63.2 years (HC). Liver metastases were present in 29% (AGT) and 33% (HC). The response rates were 11% (AGT) and 21% (HC). At 12 months the failure of treatment rate was 80% (AGT) and 70% (HC). Survival at 12 months was 50% for both groups. At 12 months 5/12 survivors were still on AGT and 8/12 on HC. These preliminary findings have so far failed to show any statistical difference in tumour response, time to treatment failure or survival between low-dose AGT and HC as second-line hormone treatment post-tamoxifen in advanced breast cancer.     

Breast cancer--a medical disease?

The treatment of breast cancer has changed significantly over the last 20 years. It is now believed that breast cancer usually spreads early and that removal of neither lymph nodes nor the breast prolongs survival, although these procedures do improve local control of the disease. Involvement of lymph nodes is prognostically important as a reflection of the body's defenses against spreading cancer cells. Systemic adjuvant therapy with tamoxifen improves survival in estrogen receptor (ER)-positive women and chemotherapy does so in ER-positive or negative women. This article gives an overview of the evolution in the treatment of breast cancer over the past 20 years, and describes the Breast Cancer Prevention Trial (BCPT) and several trials of adjuvant therapy which are now being conducted by the National Surgical Adjuvant Breast Project (NSABP).     

Positron emission tomography with 2-[18F]Fluoro-2-deoxy-D-glucose and 16alpha-[18F]fluoro-17beta-estradiol in breast cancer: correlation with estrogen receptor status and response to systemic therapy

We assessed the value of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and 16alpha-[18F]fluoro-17beta-estradiol (FES) in women with breast cancer for predicting response to systemic therapy. Results of FES-PET were correlated with estrogen receptor (ER) status. Forty-three women with locally advanced or metastatic breast cancer underwent FDG-PET and FES-PET prior to institution of systemic therapy. All patients had measurable disease and had tumors submitted for ER determination. Cancers were considered functionally hormone sensitive if the standardized uptake value of the lesion on FES-PET was >/=1.0 (FES+) and hormone resistant if the standardized uptake value was <1.0 (FES-). Information obtained by FES-PET was compared with the results of ER assays. The tumor response to chemotherapy and hormonal therapy was correlated with intensity of uptake by both FDG-PET and FES-PET. The ER status of the breast cancers was negative (ER-) in 20 patients, positive (ER+) in 21 patients, and unknown in 2 patients. All 20 of the ER- tumors were also FES-. However, of the 21 ER+ tumors, 16 were FES+ and 5 were FES-. Thirty patients were treated initially with chemotherapy, and 21 (70%) demonstrated objective responses. We were unable to correlate the response to chemotherapy with information obtained by FDG-PET or FES-PET. Thirteen patients were treated with hormone therapy, and 8 (61%) responded to that therapy. Only 1 of the 5 patients whose tumors were ER+ but FES- received hormone therapy, and this treatment resulted in disease stabilization only. Multiple sites of disease were assessed by FES-PET in 17 patients with metastatic breast cancer. Functional hormone sensitivity, defined by FES-PET, was concordant with multiple lesions in 13 (76%). Ten patients with locally advanced breast cancer developed recurrent disease. The initial site of recurrence was the breast in 5 patients. Of the 5 patients with systemic recurrence, 4 had disease detected at the site of recurrence on the pretreatment FDG-PET study but not detected on pretreatment computed tomography. In our experience, FDG-PET imaging is more sensitive than conventional imaging methods, including computed tomography, in staging women with breast cancer. When compared with the in vitro assay of ER status, FES-PET has an apparent sensitivity of 76% and specificity of 100%. Our finding of a subset of patients who have tumors that are ER+ and FES- suggests that the functional assessment of hormone sensitivity by PET imaging can identify patients with ER+ disease whose tumors are likely to be hormone refractory.     

Safety, activity and estrogen inhibition by exemestane in postmenopausal women with advanced breast cancer: a phase I study

Exemestane is an irreversible, steroidal, oral aromatase inhibitor under evaluation in postmenopausal women with advanced breast cancer. A phase I study was conducted in 27 postmenopausal patients who were candidates for hormone therapy because they had advanced breast cancer and estrogen receptor-positive or unknown status. Most patients were moderately or heavily pretreated. Cohorts of at least three patients received sequentially escalating daily oral doses of 5-600 mg. The median duration of exemestane treatment was 13 weeks (range: 3-166 weeks). The maximal tolerated dose was not reached because of lack of treatment-related grade 3 or 4 toxicity. The most common adverse events, including those not related to treatment, were mild to moderate headache (44% of patients), dizziness (33%), nausea (33%), hot flushes (30%) and tumor-related pain (30%). There were three complete and four partial responses for an objective response rate of 26% (95% CI: 11.1-46.3%) in the intent-to-treat population; the median duration of response was 74 weeks (95% CI: 48-99 weeks). Exemestane, at the dose of 25 mg, maximally suppressed estradiol, estrone and estrone sulfate serum levels to 13, 5 and 10% of baseline, respectively. Exemestane appears to suppress estrogen, be well tolerated and have antitumor activity in postmenopausal women with advanced breast cancer. A large, safe therapeutic window of up to 600 mg was defined. In view of its safety and estrogen-suppression profiles, the most favorable effects were observed at the 25 mg daily dose.     

Prediction of recurrence for advanced breast cancer. Traditional and contemporary pathologic and molecular markers

Approximately 50% of patient with breast cancer ultimately develop metastases, among which only 10% to 15% of patients live 5 years or more. Patients with locally advanced (stage III) breast cancer have a 5-year survival rate of approximately 20% to 30%. Thus, despite high remission rates obtained with current therapies, the poor long-term results associated with the apparent plateau of response achievable with systemic therapies emphasize the necessity of identifying accurate prognostic factors for this group of patients. This will allow an informed discussion with the individual patient. In addition, prognostic information could be used to guide the therapy and also to identify those subgroups of patients who may benefit with less-aggressive therapies. Furthermore, in the context of randomized studies, prognostic factors can be used to stratify patients. Prognostic factors have been extensively studied in early-stage breast cancer. In comparison, only a few studies exist on biologic prognostic factors in advanced breast cancer. Based on the limited information available, it appears that the biologic factors prognostic for locally advanced breast cancer are similar to those reported for early-stage breast cancer. Apparently, certain factors have a prognostic value irrespective of the stage of the disease at the time of presentation. This would then suggest that certain factors maintain their significance as the breast cancer progresses from an overtly local to a systemic disease. It is already well recognized that histologic grade is a significant prognostic factor for early-stage as well as metastatic breast disease. Hormone receptors have been reported to be of prognostic value at all stages of disease. Proliferation rate assessed by a variety of techniques as well as determination of the Nottingham Primary Prognostic Index provides important information about the rate of the growth of the tumor. Thymidine labeling index and S-phase fraction also provide information in regard to response to chemotherapy. DNA ploidy has been reported to be of significance in prediction of response to adjuvant chemotherapy and to a lesser extent to hormone therapy. The value of DNA ploidy in relation to survival in advanced breast cancer, however, remains controversial. Other prognostic factors such as oncogenes, tumor suppressor genes, and growth factors have also shown some predictive value in advanced breast cancer. Similar to what has also been suggested in early breast cancer, much research still needs to be done to clarify the role of currently available prognostic factors and to identify new, more powerful discriminants.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hormonal replacement therapy and breast cancer]

Hormonal replacement therapy is prescribed more and more frequently to increase quality of life and decrease the symptomatic and organic consequences of the menopausal status. The different studies which analyzed the risk of breast cancer for women under hormonal replacement therapy show opposed conclusion. We reviewed articles published between 1980 and 1997 to try to conclude about the consequences of the action of this treatment in the risk of breast cancer from the characteristic of the hormonal replacement therapy and from known risk of breast cancer. Hormonal replacement therapy increases the incidence of breast cancer. Risk increase with the treatment duration and a low estrogen dose would be sufficient to palliate to the hormonal lack (< 0.625 mg/j). The risk of breast cancer becomes the same that this of women without hormonal replacement treatment when treatment interrupted. The association of estrogen and progestin should not be protective of breast cancer. But the hormonal treatment seems to be synergistic for the risk of breast cancer with late menopause, late age at the birth of first child. Hormonal treatment could increase the estrogenic period and should increased the risk of breast cancer in women with late age at menarche, late age at menopause and late age at first child. It should not increase the risk of breast cancer in women with benign breast disease, with family history of breast cancer and in nulliparous women. For women who undergone a bilateral oophorectomy before hormonal replacement treatment the risk would be the same than for women with natural menopause and without hormonal replacement treatment. However breast cancer should be diagnosed earlier in women with hormonal treatment because mammographies were made more frequently. Overall survival should not different between the women who were under hormonal therapy and theses were not.     

Social support and survival among women with breast cancer

BACKGROUND: Two recently reported randomized trials, one among patients with advanced breast cancer and the other among patients with early stage melanoma, suggested that social support may affect survival favorably. This study assesses relationships of social support indicators with 7-year survival among women diagnosed with localized or regional stage breast cancer. METHODS: All newly diagnosed patients with surgically treated localized or regional disease in seven Quebec City hospitals in 1984 were considered for this analysis. Among 235 eligible patients, 224 (95%) participated in a home interview 3 months after surgery. This interview provided information on the use of confidants in the 3 months after surgery. Data on disease and treatment characteristics were abstracted from patients' medical records. RESULTS: Compared with women who used no confidant in the 3 months after surgery, the hazard ratio for the 7-year period was 0.61 (95% confidence interval [CI], 0.33-1.12) among those who had used at least one confidant, 0.54 (95% CI, 0.28-1.06) in women who used two or more types of confidant, and 0.51 (95% CI, 0.22-1.18) among those whose confidants included either physician or nurse. These results were adjusted for age, presence of invaded axillary lymph nodes, adjuvant radiotherapy, and adjuvant systemic therapy (hormone or chemotherapy). CONCLUSION: These results support the view that social support may be associated with longer survival among women with localized or regional stage breast cancer.