Treatment Of Operable Breast Cancer Research Articles

Phase II randomized trial of docetaxel (D) monotherapy vs epirubicin plus docetaxel (ED) as neoadjuvant treatment of operable breast cancer (BC)

599 Background: The combination of E and D has demonstrated clinical objective response rates (ORR) of up to 81% as neoadjuvant therapy for operable BC (Luporsi, ASCO 2000). The RR for D monotherapy in this setting has been up to72% (Amat, ASCO 2000). This phase II trial evaluated the pCR of D vs ED in the neoadjuvant setting. Methods: Eligible patients (pts) with histologically proven unilateral BC, unilateral, T2-T3, M0, clinically and radiologically measurable lesions ≥3 cm, adequate heart and organ functions and conservative surgery rate were randomized to 3-weekly treatment with either D 100mg/m2 maximum 8 cycles or E 100 mg/m2+D 75mg/m2+G-CSF, maximum 6 cycles. The primary endpoint was the pCR rate; secondary endpoints were clinical and radiological RR, rate of breast conserving surgery, relapse free survival, and safety. Results: From February 2001 to June 2003, we treated 31 pts with D and 29 pts with ED, with a respective median age 48.6 (30.2–65.8) and 51.7 (29.8–63.6) years and median tumour diameter 6(3–11) and 5(3–10) cm. To date, 29 pts (D) vs 27 pts (ED) were evaluable for clinical response: ORR was respectively 82.8% (34.5%CR, 48.3%PR) vs 88.9% (29.6%CR, 59.3%PR). The radiological ORR was evaluated in 21 (D) vs 16 (ED) pts, with ORR 80.9% (23.8%CR, 57.1%PR) vs 68.8% (12.5%CR, 56.3%PR), respectively. pCR (Chevallier classification) was 18% with (D) among 22 evaluated pts vs 10% with (ED) among 20 evaluated pts. Using the Salatoff classification, pCR was 19% with (D) among 21 evaluated pts vs 16% with (ED) among 19 evaluated pts. Grade 3–4 toxicities (% pts) were (D, ED, respectively): febrile neutropenia (0, 3.7), neutropenia (93, 70), asthenia (16.7, 11) and nail disorders (13, 3.7). Conclusions: This preliminary analysis suggests that D monotherapy (100mg/m2) for 8 cycles is at least as good as ED combination therapy for 6 cycles when used as neoadjuvant treatment for operable BC. No significant financial relationships to disclose.

Phase II randomized trial of docetaxel (D) monotherapy vs epirubicin plus docetaxel (ED) as neoadjuvant treatment of operable breast cancer (BC)

Phase II randomized trial of docetaxel (D) monotherapy vs epirubicin plus docetaxel (ED) as neoadjuvant treatment of operable breast cancer (BC)

Oral clodronate for adjuvant treatment of operable breast cancer: Results of a randomized, double-blind, placebo-controlled multicenter trial

528 Background: The bisphosphonate clodronate (Bonefos) may reduce the incidence of bone metastases by inhibiting tumor-induced osteoclastic resorption of bone. Methods: This randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of oral clodronate in 1,069 patients with primary operable stage I-III breast cancer from 1989–2000. Patients received oral clodronate (1600 mg/day) or placebo for 2 years, starting within 6 months of primary treatment (surgery, radiotherapy, and tamoxifen). Ad hoc analyses from this study have been published previously (Powles et al. JCO 2002), and the unpublished protocol-specified results and ad hoc analysis of stage II/III patients are reported here. The protocol-specified primary endpoint was time to first bone metastasis during the 5-year study period. The secondary endpoint was overall survival. These endpoints were analyzed by unstratified Log-rank test and hazard ratio (HR) with 95% CI. Results: Patient demographics were similar between treatment groups. Oral clodronate significantly reduced the risk of bone metastases by 45% in all patients during the medication period (2 years: HR = 0.546, P = 0.031), and by 31% during the study period (5 years: HR = 0.692, P = 0.043) compared to placebo. Similarly, clodronate significantly reduced the risk of bone metastases in patients with stage II/III disease during the medication (2 years: 50%, HR = 0.496, P = 0.020) and study (5 years: 41%, HR = 0.592, P = 0.009) periods. Oral clodronate vs. placebo significantly improved overall survival (23% reduction in risk of death: HR = 0.768, P = 0.048) and survival for stage II/III patients (26% reduction in risk of death: HR = 0.743, P = 0.041). Oral clodronate was well tolerated, with mild-to-moderate diarrhea being the most frequently reported adverse event. Conclusion: In patients with primary operable breast cancer, oral clodronate significantly reduced the risk of bone metastases and significantly improved survival rates during the medication and 5-year study periods compared to placebo. Similar results were seen in stage II/III patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering OY Schering AG Schering AG; Schering Oy Leiras Oy

FDG-PET for axillary lymph node staging in primary breast cancer.

Management of the axilla in patients with operable breast cancer is still one of the most controversial areas in clinical oncology. The best procedure to examine the lymph nodes is still standard axillary lymph node dissection; nevertheless, the morbidity associated with this procedure is well known. Based on these considerations, it is important for progress in the treatment of operable breast cancer that strategies are found that permit a less invasive method of axillary sampling which does not impair the patient's quality of life. The technique of sentinel lymph node (SLN) biopsy has recently been proposed for this purpose, with very important results. SLN has now become routine practice in the surgical management of breast cancer, and in many institutions patients with a negative SLN biopsy are spared axillary dissection, while those with a positive SLN biopsy are submitted to axillary node dissection. The good accuracy of SLN biopsy represents a significant advance in the management of primary breast cancer; however, false negative axillary results can occur in a variable percentage of patients, and the contribution of the SLN procedure to the detection of metastases in the internal mammary and supraclavicular lymph nodes is not clear. Among the recently developed imaging modalities, positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has in particular been applied to the study of lymph node metastases in cancer patients. Several clinical studies have been carried out to evaluate the accuracy of PET in the axillary staging of operable primary breast cancer. These studies have sometimes provided conflicting results, either supporting the possibility of using FDG-PET to select patients who need axillary dissection or questioning whether FDG-PET can accurately assess the axillary status in primary breast cancer. All the limitations and the advantages of FDG-PET are discussed in this paper, by examining the performance of scanner technology and the possible causes of the false negative results. In the experience of the authors, comparing FDG-PET with SLN biopsy in the same series of patients, the results seem to indicate that the lower sensitivity of PET is restricted to micrometastases. Of course, this limitation of PET has to be analysed in relation to the importance of such small axillary metastases for the outcome of patients with breast cancer. The added value offered by PET in breast cancer staging in comparison with intraoperative detection of the sentinel node lies in the fact that FDG-PET is a non-invasive procedure that allows, within a single examination, the biological characterisation of breast cancer and viewing of the entire body.

Docetaxel in the Treatment of Operable Breast Cancer

Docetaxel in the Treatment of Operable Breast Cancer

Docetaxel in the Treatment of Operable Breast Cancer

Docetaxel in the Treatment of Operable Breast Cancer

International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations.

Primary systemic therapy (PST) represents the standard of care in patients with locally advanced breast cancer. In addition, there is increasing information on PST in operable breast disease that supports the use of PST in routine practice. However, current regimens and techniques vary. To address this concern, a group of representatives from breast cancer clinical research groups in France, Germany, Italy, the United Kingdom, and the United States reviewed all available data on prospective randomized trials in this setting. Recommendations are made regarding terminology, indications, regimen, diagnosis before treatment, monitoring of efficacy, tumor localization, surgery, pathologic evaluation, and postoperative treatment.

Paravertebral block anesthesia for inguinal hernia repair.

Choice of anesthesia for inguinal hernia repair remains a controversial topic. Local anesthesia has been described in the literature as the optimal technique, however general and spinal anesthesia are commonly used in practice despite well-known complications and side effects. The regional technique of paravertebral block has been successfully used at our institution for the operative treatment of breast cancer. Its attributes are prolonged sensory block with minimization of postoperative pain, reduction of nausea and vomiting, shortened hospital stay, patient satisfaction, and rapid return to normal activities. These features are desirable in the practice of ambulatory hernia surgery; hence we initiated the use of thoracic/lumbar paravertebral block for that surgical procedure. Paravertebral block anesthesia was performed on 30 consecutive patients. Block placement took an average of 12.3 minutes, in six cases repeat injection at one or two spinal levels was required due to incomplete blockade. Paravertebral block achieved effective anesthesia in 28 of 30 cases; conversion to general anesthesia was performed for two failed blocks. We are reporting postoperative data on the 28 completed blocks. Supplementation of intravenous sedation or injection of local anesthesia successfully treated transient intraoperative pain in 10 cases. Epidural extension of anesthesia resulting in lower limb numbness and motor weakness delayed the discharge of two patients. There were no other complications of anesthesia and no cases of urinary retention. TIme to onset of pain averaged 15 hours, while duration of sensory block was 13 hours. Patients were prescribed a standing order of naproxen 500 mg B.I.D. for 4 days regardless of pain; supplemental oral narcotic use during the 48 hours following surgery averaged 3.5 tablets, with 6 patients not requiring any narcotic. ninety-six percent of patients scheduled for ambulatory surgery were discharged from the postanesthesia care unit, with an average stay of 2.5 hours. Employed patients returned to work on day 5.5 (range 3-10 days); patients who were not employed returned to regular activities in 5.8 days (range 1-14 days). Eighty-two percent of patients reported being "very satisfied" with the anesthetic technique.

Treatment of operable breast cancer in the elderly: a randomised clinical trial EORTC 10850 comparing modified radical mastectomy with tumorectomy plus tamoxifen

We have examined the outcome of older patients with operable breast cancer treated in a randomised trial by either standard surgery or less extensive surgery and tamoxifen. There were 236 participants aged ⩾70 years, randomised to either modified radical mastectomy MRM ( n=120) or wide local excision (WLE) and tamoxifen (T) 20 mg daily ( n=116). Survival curves were estimated using the Kaplan–Meier method and multivariate analyses were performed using Cox's proportional hazards model. Endpoints were survival and time to first relapse or progression, loco-regional progression, time to distant progression and progression-free survival. No significant difference was seen in terms of progression-free survival, but there were significantly more loco-regional relapses in the WLE+T group. In contrast, there were more distant metastases in the MRM group, but with a similar overall survival in both groups. The results of this trial give cautious support for the use of WLE+T for selected older women.

Treatment of operable breast cancer in the elderly: a randomised clinical trial EORTC 10851 comparing tamoxifen alone with modified radical mastectomy

For treatment of early breast cancer in older women, little evidence is available from randomised trials. We conducted a randomised trial comparing modified radical mastectomy (MRM) with tamoxifen (TAM) as the sole initial therapy in 164 patients aged ⩾70 years with operable breast cancer. 82 were treated by MRM and 82 with TAM. Survival curves were estimated using the Kaplan–Meier method: multivariate analyses were performed using the Cox's proportional hazards model. Endpoints included survival, time to first relapse or progression, loco-regional progression, time to distant progression and progression-free survival. After a median follow-up of approximately 10 years, there was a significantly decreased time to progression in the TAM only group (logrank P<0.0001) and significantly shorter time to local progression within the TAM group (logrank P<0.0001). Overall survival of the two groups was similar. The results indicate that tamoxifen alone leads to an unacceptably high rate of local progression or relapse.

The curative role of radiotherapy in the treatment of operable breast cancer

The last quarter of the twentieth century has brought about sweeping changes in the loco-regional treatment of breast cancer. Randomised trials have consistently established that survival rates after conservation surgery and breast irradiation are equivalent to those observed after modified radical mastectomy [1]. Moreover, during the same period the use of mammography in asymptomatic women has led to a relative increase in small tumours, ideally suitable for breast conservation. As a consequence, the use of conservation surgery has risen progressively during the 1980s and 1990s, with a corresponding increase in the importance of breast irradiation. In addition, recent meta-analyses of randomised trials have established that breast cancer mortality can be significantly reduced by loco-regional radiotherapy (RT), and that the increased intercurrent mortality observed in older trials was caused by an excess in cardiovascular deaths, presumably avoidable, associated with the earlier techniques [2,3]. Newer trials of postmastectomy radiotherapy (PMRT) have demonstrated a clear survival improvement, without excess cardiac morbidity, leading to an increased confidence in the use of adjuvant loco-regional RT [4,5]. The extent of the swing to conservative surgery varies amongst geographical regions, depending, at least in part, on the availability of radiotherapy services. With the increasing diffusion of medical technology throughout Europe, this factor will probably assume a decreasing importance for the choice of primary breast cancer therapy. In urban areas with a high socio-economic standard, it is likely that mastectomy will come to be practised in a dwindling minority of patients. According to the Geneva Tumour Registry, the proportion of all curative breast operations that were conservative rose from 3% before 1985, to 51% in 1990, then to 67% since 1998 (Registre genevois des tumeurs, unpublished data, 2000). As a consequence, patients currently requiring mastectomy are likely to have larger tumours and positive lymph nodes, and will frequently be considered for PMRT. In such a setting, a substantial majority of primary breast cancer patients will therefore receive RT as part of their initial treatment. These changes come at a time when the prevalence of breast cancer is increasing significantly due, at least partly, to the ageing of the European population. For Geneva, an increase of more than 50% in the number of new breast cancer cases is projected for the period between 2000 and 2010 (Registre genevois des tumeurs, unpublished data, 1998). The demand for radiotherapy services required to treat breast cancer patients may thus be expected to increase substantially. Accordingly, the European Society of Mastology (EUSOMA) believes that a position paper regarding the use of RT in breast cancer is timely and useful. This document discusses the indications for adjuvant RT in operable breast cancer (clinical stages T0-3, N0-1, M0), the technical principles for its proper execution, and where possible, notions of its optimal co-ordination with other treatment modalities. As the breast cancer literature is vast, analysis was necessarily restricted to data having a high likelihood of being reliable, making every effort to draw conclusions likely to be pertinent to

Reduced use of drains following axillary lymphadenectomy for breast cancer.

Axillary dissection is frequently performed during the treatment of operable breast cancer, and is associated with certain morbidities. Accumulation of axillary fluid, otherwise known as a seroma, is a frequent complication that appears to be related to the degree of dissection. Based on empirical evidence, surgeons have attempted to reduce the occurrence and duration of seromas by using suction drainage, but this concept has been challenged by several authors. To determine if the natural history of seroma fluid accumulation after axillary surgery is altered by the duration of suction drainage or non-placement of a drain. Ninety consecutive patients having axillary dissection for breast cancer had either prolonged suction drainage (mean 9.6 days), short duration drainage (2 days), or had no drain placed. Seromas were aspirated and the time to cessation of fluid accumulation determined, as well as any other wound complications. There was no difference in the number of wound complications or the duration of fluid accumulation between the three groups, being 26.6, 25.7, and 27.9 days, respectively. Patients having no drains placed required more frequent aspirations. The duration of seroma fluid accumulation is not altered by the placement of a suction drain following axillary lymphadenectomy.

Radical surgery with omental flap for uncontrolled locally recurrent breast cancer.

Uncontrolled chest wall disease due to breast cancer is a highly morbid condition causing pain, ulceration, malodour and the need for frequent dressings. Aggressive surgical approaches are rarely justified because most patients will succumb to metastatic breast cancer within a short period. A highly selected group of patients with minimal or no evidence of metastatic disease and good performance status may benefit from radical chest wall surgery. Omental transposition flaps are ideal for reconstructing extensive surgical defects following chest wall surgery. A retrospective review was carried out of 61 female patients treated consecutively between 1980 and 1995. The surgical technique is described herein. All patients were symptomatic preoperatively. Symptoms included ulceration (80%), pain (44%) and malodour (40%). Twenty-nine patients had uncontrolled local recurrence following initial treatment for locally advanced breast cancer and 32 patients developed uncontrolled recurrence after treatment for operable breast cancer by mastectomy or conservation surgery. Median survival following chest wall surgery was 21 months and the median local recurrence-free interval was 20 months. Morbidity was -limited. There were no cases of major flap loss. Twenty-nine patients (48%) had no further local disease. Eighteen patients (30%) developed soft-tissue recurrence at the edge of the omental flap or in surrounding skin and 14 (23%) developed recurrence beneath the flap. In a highly selected group of patients with symptomatic uncontrolled chest wall recurrence who are fit and have an expectation of at least moderate-term survival, radical chest wall surgery and omental flap transposition offers excellent palliation and local control in the majority of patients

Optimal control for a stochastic model of cancer chemotherapy

Chemotherapy is useful in a number of cancers to reduce or eliminate residual disease. When used in this way the objective is to maximise the likelihood that the cancer will be eliminated. In this article, we extend a stochastic model of chemotherapy for cancer to incorporate its concomitant effect on the normal system and derive overall measures of outcome. The model includes the development of drug resistance and is sufficiently flexible to include a variety of tumour and normal system growth functions. The model is then applied to situations previously examined in the literature and it is shown that early intensification is a common feature of successful regimens in situations where drug resistance is likely. The model is also applied to data collected from clinical trials analysing the effect of adriamycin, and cyclophosphamide, methotrexate and 5-flourouracil (CMF) therapy in the treatment of operable breast cancer. The model is able to mimic the data and provides a description of the optimal regimen.

Adjuvant systemic treatment for operable breast cancer — Standard therapies and new approaches

Adjuvant systemic treatment for operable breast cancer — Standard therapies and new approaches

Use of paravertebral block anesthesia in the surgical management of breast cancer: experience in 156 cases.

To assess safety and efficacy of the regional anesthetic technique paravertebral block for operative treatment of breast cancer, and to compare postoperative pain, nausea, vomiting, and length of hospital stay in patients undergoing breast surgery using paravertebral block and general anesthesia. General anesthesia is currently the standard technique used for surgical treatment of breast cancer. Increasing hospital costs have focused attention on reducing the length of hospital stay for these patients. However, the side effects and complications of general anesthesia preclude ambulatory surgery for most patients undergoing breast surgery. In April 1994, the authors initiated the use of paravertebral block anesthesia for patients undergoing primary breast cancer surgery. A review of our early experience revealed that this regional anesthetic technique enables effective anesthesia for operative procedures of the breast and axilla, reduces postoperative nausea and vomiting, and provides prolonged postoperative sensory block that minimizes narcotic requirements. A retrospective analysis of 145 consecutive patients undergoing 156 breast cancer operations using paravertebral block and 100 patients undergoing general anesthesia during a 2-year period was performed. Anesthetic effectiveness and complications, inpatient experience with postoperative pain, nausea, vomiting, and length of stay were measured. Surgery was successfully completed in 85% of the cases attempted by using paravertebral block alone, and in 91% of the cases, surgery was completed by using paravertebral block supplemented with local anesthetic. There was a 2.6% incidence of complications associated with block placement. Twenty percent of patients in the paravertebral group required medication for nausea and vomiting during their hospital stay compared with 39% in the general anesthesia group. Narcotic analgesia was required in 98% of general anesthesia patients, as opposed to 25% of patients undergoing paravertebral block. Ninety-six percent of patients having paravertebral block anesthesia were discharged within the day of surgery, compared with 76% of patients who had a general anesthetic. Paravertebral block can be used to perform major operations for breast cancer with minimal complications and a low rate of conversion to general anesthesia. Paravertebral block markedly improves the quality of recovery after breast cancer surgery and provides the patient with the option of ambulatory discharge.

Proposal for a new model of breast cancer metastatic development

The commonly accepted theory of breast cancer metastatic development assumes continuous tumor growth from tumor seeding until documentation of clinical recurrence. In particular, Gompertzian growth kinetics is currently the theoretical cornerstone of the natural history of breast cancer, and has been widely utilized for planning treatments. To verify agreement between findings and the implications of the continuous growth model, several published papers about the natural history of breast cancer after removal of the primary tumor were reviewed. Also, findings from animal models concerning metastasis biology were considered. The continuous growth model failed in important ways upon this critical reappraisal. As an alternative, the tumor dormancy hypothesis was considered to provide a more reasonable description of tumor recurrence. Moreover, primary tumor removal was revealed as a potentially perturbing factor for metastasis development. A new general outline of metastatic development of breast cancer incorporating tumor dormancy in specific micrometastatic phases, stochastic transitions between them, and start signals from surgery for micrometastatic growth was designed. The proposed model suggests new views concerning scheduling of current chemotherapy, new treatment approaches aimed at keeping micrometastases in a dormant state for the patient's entire life, and the careful reappraisal of the timing of surgery within the multimodal treatment of operable breast cancer.

Inadequacy of iridium implant as sole radiation treatment for operable breast cancer

In order to avoid a prolonged course of external irradiation as part of breast conservation therapy, 27 patients received an iridium implant to the primary tumour bed as sole radiation treatment. Surgery was standardised comprising tumourectomy and axillary clearance. Using a rigid implant afterloading with iridium192 wires, 55 Gy was delivered on a continuous basis over 5 days. After 6 years median follow-up, relapse of cancer within the treated breast has occurred in 10 of the 27 patients (37%). Compared with historical controls treated by similar surgery and iridium192 implant (20 Gy) with external radiotherapy (46 Gy), there was a significantly increased breast relapse rate in those treated by iridium implant alone. However, the incidence of distant metastases and overall survival was similar. Thus, a continuous iridium192 implant delivering 55 Gy in 5 days is not an effective means of achieving local control in patients with operable breast cancer.

SY-6-1 Treatment of operable breast cancer in the elderly

SY-6-1 Treatment of operable breast cancer in the elderly

Conservative treatment of breast cancer: Milan experience

Background The conservative treatment of operable breast cancer has gradually become well-established during the last 20 years as it offers adequate loco-regional control of the disease and saves the brest. Moreover, larger, demolishing operations have not shown to decrease the risk of distant metastases.