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PubMed2000

Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.

Adult↗
PubMed2002

Vitamin D and systemic therapy.

The most frequently used systemic treatments for severe psoriasis are methotrexate (MTX), oral retinoids, and cyclosporine; however, all of these agents are associated with dose-related toxicities that limit their use. The safety and efficacy of topical calcipotriene for the treatment of psoriasis have been demonstrated in numerous clinical studies. The rationale for using calcipotriene in combination with systemic therapies is based on their different modes of action and nonoverlapping side effects. Three controlled clinical trials have demonstrated that the addition of calcipotriene ointment to systemic antipsoriatic treatment with MTX, acitretin, and cyclosporine increases the therapeutic efficacy compared with systemic therapy alone and minimizes side effects by either reducing the dosage or duration of treatment.

Acitretin↗
PubMed2000

Systemic therapy.

Our knowledge base on systemic therapy for breast cancer continues to expand, including further information regarding hormonal prevention in high-risk women, beneficial effects of tamoxifen in noninvasive disease, an update on primary systemic therapy, and optimization of adjuvant strategies, including data on adjuvant chemoendocrine regimens. The proper evaluation of high-dose strategies has been jeopardized by a serious episode of scientific misconduct. New data are also available on palliative options, bisphosphonates, antibody therapies, and novel targets. Data continue to evolve on the role and optimal schedules of taxanes in early-stage and advanced breast cancer. These and other important recent findings are discussed in this review article.

Antibodies, Monoclonal↗
PubMed2005

[Experimental study of dually targeting gene therapy system for pituitary adenomas].

OBJECTIVE: To construct a dually targeting gene therapy system for pituitary adenomas and investigate its effect. METHODS: Promoter hGHp containing human growth hormone gene was obtained from human genome and cloned into the plasmid pcDNA3.1/His A with the promoter cut to construct the recombinant plasmid pcDNA3.1/His A-hGHp. HSV-TK gene was obtained from the plasmid pcDNA3.1/His A-TK and integrated into the plasmid pcDNA3.1/His A-hGHp to construct the recombinant plasmid pcDNA3.1/His A-hGHp-TK. A GE7 gene delivery system-mediated human growth hormone promoter controlled gene therapy system was constructed by adding the mixture of GE7-polylysine and HA20-polylysine into the DNA solution. Human growth hormone-secreting pituitary adenoma cells of the GH3 line, human myeloma cells of the U-2OS line, and human oophoroma cells of the HO8910PM line were cultured and transfected with PBS or GE7 packaged pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK. Western blotting was used to examine the expression of PBS or GE7 packaged pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK protein, MTT method was used to detect the cell survival rate. Another GH3, U-2OS, and HO8910PM cells were cultured and transfected with PBS or GE7 packaged pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK and then ganciclovir (GCV) was added. MTT method was used to examine the cell survival rates. GH3 cells were injected subcutaneously into the right axilla of 200 SD nude rats loaded with human pituitary adenoma. Three weeks after the rats were randomly divided into 5 equal groups: PBS group in which PBS was injected into the tumor and GCV was injected peritoneally; GE7 group in which GE7-polylysine and HA20-polylysine were injected into the tumor and GCV was injected peritoneally; without TK group in which GE7-packaged pcDNA3.1/His A-hGHp was injected into the tumor and GCV was injected peritoneally; without GCV group in which GE7-packaged pcDNA3.1/His A-hGHp-TK was injected into the tumor and PBS was injected peritoneally; and treatment group in which GE7-packaged pcDNA3.1/His A-hGHp-TK was injected into the tumor and GCV was injected peritoneally. Peritoneal injection lasted 21 days for all groups. On the days 3, 7, 14, and 21 eight rats from each group were killed to measure the volume of tumor. The survival rate of the rest 8 rats was observed. RESULTS: A dually targeting gene therapy system for pituitary adenoma was composed successfully. HSV-TK protein was expressed in the GH3 cells but not in the U-2OS and HO8910PM cells after transfection of GE7-packaged pcDNA3.1/HisA-hGHp-TK; and was expressed in the GH3 and HO8910PM cells but not in the U-2OS cells after transfection of GE7-packaged pcDNA3.1/HisA-TK. Transfection of GE7-packaged pcDNA3.1/HisA-hGHp-TK and addition of GCV significantly decreased the survival rate of the GH3 cells, but did not influence the survival rates of the U-2OS and HO8910PM cells. Transfection of GE7-packaged pcDNA3.1/HisA-TK and addition of GCV significantly decreased the survival rate of GH3 and HO8910PM cells but did not influence the survival of the U-2OS and HO8910PM cells. When the GH3 cells were transfected with GE7-packaged pcDNA3.1/HisA-hGHp-TK with the addition of GCV of the concentration of 4 mg/L the survival rate decreased to 10%, when the GCV concentration was raised to 8 mg/L the survival rate of the GH3 cells was < 5%. Three days after the beginning of treatment the tumor volume of different groups of rats increased at different degrees and the tumor was smallest in the treatment group in comparison with the other groups (all P < 0.05). Seven days after the beginning of treatment the tumor volume of the treatment group significantly decreased and the tumors of the other groups still increased (all P < 0.001). The survival time of the treatment group was over 120 days, significantly longer than those of the other groups (all about 40 days). CONCLUSION: GE7 system-mediated hGHp controlled gene therapy system is hopeful to be the targeted therapeutic strategy for pituitary adenomas.

Adenoma↗
PubMed1995

Prospective randomized study of surgical morbidity following primary systemic therapy for breast cancer.

The influence of primary systemic therapy in treating operable breast cancer on postmastectomy morbidity rates was investigated. The contribution of other risk factors was assessed by multiple logistic regression. Seventy-nine eligible patients were randomly allocated, 39 to undergo immediate modified radical mastectomy, and 40 to receive initial cytotoxic or endocrine treatment followed by mastectomy. Postoperative wound seroma, infection and necrosis were recorded prospectively. Fourteen minor and six major complications occurred in 17 patients treated conventionally, while 14 patients developed 11 minor and six major complications after systemic therapy (P > 0.4). Median hospital stay was 8 days for both groups. Age, smoking, immediate breast reconstruction and the type of primary systemic treatment given were not independent predictors of complication risk. Obesity emerged as a significant risk factor for postmastectomy complications (P = 0.015). Primary systemic therapy does not increase the rate of morbidity after mastectomy.

Adult↗
PubMed2003

MammoSite radiation therapy system.

The MammoSite Radiation Therapy System (RTS) has become the most widely used brachytherapy method used in the treatment of breast cancer, due to its ease of use, short learning curve, and requirement of only one interstitial path through the breast skin. The dosimetry is simple, one source position in the middle of the MammoSite balloon catheter. The data on long-term complications, however are not available, though developing. Trials for DCIS are being developed, as well as a comparison trial to standard external beam radiation as well as other forms of accelerated partial breast irradiation (APBI).

Brachytherapy↗
PubMed1993

Adjuvant systemic therapy in breast cancer.

Systemic adjuvant therapy has improved the prognosis of patients with primary breast cancer. Meta-analyses have demonstrated that approximately one fourth of deaths can be avoided among younger women treated with multiple cytotoxic drug regimens and among older women treated with tamoxifen. However, with the treatments available today many aspects related to the optimal therapy, taking into account the physical, psychological and socioeconomic consequences, are still open. This review discusses some of the major open questions related to the effectiveness of the adjuvant systemic therapy in terms of its ability to reduce recurrence rate and mortality.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Primary systemic therapy of breast cancer.

Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a complete pathological response (pCR), and reduce the extent of surgery. The multitude of clinical trials using PST in breast cancer patients has not proven the fundamental hypotheses of improved overall survival and disease-free survival that drove the investigation of PST. The other potential advantages of PST, which include increasing the rate of breast-conserving surgery and predicting outcome to a particular chemotherapy regimen, are also not conclusively established. We examined the published literature on PST for breast cancer and predominantly focused our review on data from large, randomized clinical trials comparing primary systemic chemotherapy with adjuvant chemotherapy, different primary systemic chemotherapy regimens, primary systemic chemotherapy with hormonal therapy, and different preoperative hormonal therapies. Although the optimal neoadjuvant chemotherapy regimen has not been established, a combination of four cycles of an anthracycline followed by four cycles of a taxane appears to produce the highest pCR rate (22%-31%). In patients with HER-2-positive breast cancer, concurrent use of neoadjuvant trastuzumab with an anthracycline-taxane combination has produced provocative results that require further confirmatory studies. Preoperative hormonal therapy is associated with low pCR rates and should be reserved for patients who are poor candidates for systemic chemotherapy. The optimal management of patients with residual disease after the administration of maximum neoadjuvant therapy remains to be defined. The surgical approach, including the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients, is evolving. Ongoing clinical trials will help identify the subset of patients who would most benefit from the use of PST, establish the most effective PST regimen, and determine the optimal multidisciplinary approach in the management of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report.

PURPOSE: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. PATIENTS AND METHODS: We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. RESULTS: Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04). CONCLUSIONS: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.

Adolescent↗
PubMed2001

Systemic therapy.

A large body of data on systemic therapy has been presented and published in the past year, including new information on primary risk reduction, patient selection for adjuvant systemic therapy, and anthracycline-analogs. New data on ongoing adjuvant trials (including taxane studies), unpublished updates from the fourth Oxford Overview in September 2000, and provocative data on ovarian ablation were important features of the November 2000 National Institutes of Health Consensus Development Conference on Adjuvant Therapy for Breast Cancer. Important new data on anti-estrogen therapy, including aromatase inhibitors and pure antiestrogens, further expand the role of the oldest targeted breast cancer therapy. Trastuzumab and other novel compounds are being investigated as single-agents and in combination with conventional systemic approaches. Discussions on the long-term effects of adjuvant therapy have taken center stage also. These and other important ongoing developments since 2000 are examined in this review article.

Antineoplastic Agents, Hormonal↗
PubMed2004

Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies.

PURPOSE: To discuss the absolute benefits from adjuvant systemic therapy knowledge of long-term outcomes and baseline risks of relapse and disease-specific survival are required. We assessed the 10-year outcomes in a population-based cohort of node-negative (N-) lymphovascular negative (LV-) early breast cancers diagnosed from 1989 to 1991 who did not receive adjuvant systemic therapy. METHODS: One thousand one hundred eighty-seven cases of pT(1-2)N(0) LV- breast cancers with a median follow-up of 10.4 years were reviewed. Kaplan-Meier survival curves for relapse free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) were compared with log-rank tests with cohorts stratified for tumor size and grade. RESULTS: The median age of this series was 62 years. Four hundred thirty tumors were < or = 1 cm in diameter (cohort 1), 507 were 1.1-2 cm (cohort 2), and 250 were 2.1 to 5 cm in diameter (cohort 3). The 10-year outcomes for cohorts 1, 2, and 3, respectively, were significantly different: RFS, 82%, 75%, and 66%; BCSS, 92%, 90%, and 77%; and OS, 79%, 78%, and 66%. Tumor grade significantly altered outcome within size cohorts, particularly in pT(1)N(0) breast cancers. CONCLUSION: This study provides detailed information on the continued relapse and breast cancer death rate to 10 years of follow-up. Specifically, without adjuvant systemic therapy, patients with LV-, N - breast cancer had a > or = 25% 10-year risk of relapse and a corresponding 10-year breast cancer death rate of > or = 10% if they had either a grade 3 tumor < or = 1 cm, a grade 2 to 3 tumor from 1.1 to 2 cm, or any grade tumor greater than 2 cm.

Adult↗
PubMed2004

The burden of illness associated with psoriasis: cost of treatment with systemic therapy and phototherapy in the US.

OBJECTIVE: To evaluate utilization and direct healthcare expenditures among psoriasis patients treated with systemic therapy and phototherapy in the United States. DESIGN: Cohort study using retrospective administrative medical claims. PATIENTS: Psoriasis patients treated with systemic therapy and phototherapy, as well as a matched cohort of non-psoriasis patients. All patients were covered by employer-sponsored insurance between 1 April 1996 and 31 December 2000. MAIN OUTCOME MEASURES: Estimated risk of hospitalization and total annual healthcare expenditures overall and by comorbidity status were compared for persons with psoriasis using systemic therapy or phototherapy and persons without psoriasis. Annualized utilization rates for hospitalizations, and use of emergency department, outpatient physician, outpatient laboratory, and outpatient pharmaceutical services were also compared across the two cohorts. RESULTS: Seventeen percent of psoriasis patients were treated with systemic therapy or phototherapy. Patients with comorbid anemia, carcinoma, diabetes, depression, GI disorders, hepatotoxicity, hypertension, and nephrotoxicity had significantly higher expenditures than non-psoriasis patients with the same comorbidities (p < or =0.05). Elevated risk of hospitalization also contributed to higher expenditures in patients treated with systemic therapy or phototherapy. Limitations of this study include those inherent in using claims data such as dependence on diagnosis coding, the fact that psoriasis severity cannot be determined directly from claims data, confounding comorbidities, and the fact that only direct healthcare expenditures were considered in this analysis. CONCLUSION: Psoriasis patients treated with systemic therapies/phototherapies have significantly more comorbidities and higher mean total healthcare expenditures compared to non-psoriasis patients. Psoriasis patients with selected comorbidities have significantly higher mean total healthcare expenditures compared to non-psoriasis persons with the same comorbidities.

Adult↗
PubMed1999

Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy.

PURPOSE: The association between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) after conservative surgery and radiation is controversial. The width of the resection margin that minimizes the risk of IBTR is unknown. While adjuvant systemic therapy may decrease the risk of an IBTR in all patients, its impact on patients with positive or close margins is largely unknown. This study examines the interaction between margin status, margin width, and adjuvant systemic therapy on the 5- and 10-year risk of IBTR after conservative surgery and radiation. METHODS AND MATERIALS: A series of 1,262 patients with clinical Stage I or II breast cancer were treated by breast-conserving surgery, axillary node dissection, and radiation between March 1979 and December 1992. The median follow-up was 6.3 years (range 0.1-15.6). The median age was 55 years (range 24-89). Clinical size was T1 in 66% and T2 in 34%. Seventy-three percent of patients were node-negative. Only 5 % of patients had tumors that were EIC-positive. Forty-one percent had a single excision, and 59% had a reexcision. The final margins were negative in 77%, positive in 12%, and close (< or = 2 mm) in 11%. The median total dose to the tumor bed was 60 Gy with negative margins, 64 Gy with close margins, and 66 Gy with positive margins. Chemotherapy +/- tamoxifen was used in 28%, tamoxifen alone in 20%, and no adjuvant systemic therapy in 52%. RESULTS: The 5-year cumulative incidence (CI) of IBTR was not significantly different between patients with negative (4%), positive (5%), or close (7%) margins. However, by 10 years, a significant difference in IBTR became apparent (negative 7%, positive 12%, close 14%, p = 0.04). There was no significant difference in IBTR when a close or positive margin was involved by invasive tumor or DCIS. Reexcision diminished the IBTR rate to 7% at 10 years if the final margin was negative; however, the highest risk was observed in patients with persistently positive (13%) or close (21%) (p = 0.02) margins. The median interval to failure was 3.7 years after no adjuvant systemic therapy, 5.0 years after chemotherapy +/- tamoxifen, and 6.7 years after tamoxifen alone. This delay to IBTR was observed in patients with close or positive margins, with little impact on the time to failure in patients with negative margins. The 5-year CI of IBTR in patients with close or positive margins was 1% with adjuvant systemic therapy and 13% with no adjuvant therapy. However, by 10 years, the CI of IBTR was similar (18% vs. 14%) due to more late failures in the patients who received adjuvant systemic therapy. CONCLUSION: A negative margin (> 2 mm) identifies patients with a very low risk of IBTR (7% at 10 years) after conservative surgery and radiation. Patients with a close margin (< or = 2 mm) are at an equal or greater risk of IBTR as with a positive margin, especially following a reexcision. A margin involved by DCIS or invasive tumor has the same increased risk of IBTR. A reexcision of an initially close or positive margin that results in a negative final margin reduces the risk of IBTR to that of an initially negative margin. A close or positive margin is associated with an increased risk of IBTR even in patients who are EIC-negative or receiving higher boost doses of radiation. The median time to IBTR is delayed; however, the CI is not significantly decreased by adjuvant systemic therapy in patients with close or positive margins-the 5 year results in these patients underestimate their ultimate risk of recurrence.

Adult↗
PubMed2000

Systemic therapy for renal cell carcinoma.

PURPOSE: We review the status of systemic therapy for patients with advanced renal cell carcinoma. MATERIALS AND METHODS: A literature search was performed on MEDLINE and CANCERLIT to identify results of systemic therapy for patients with renal cell carcinoma published from January 1990 through December 1998. Treatment results of chemotherapy agents, immunotherapy, combination programs and adjuvant therapy were reviewed. RESULTS: No chemotherapy agent has produced response rates that justify its use as a single agent. Interferon-alpha and interleukin (IL)-2 demonstrated low response rates ranging from 10% to 20%. The results of 2 randomized trials suggest that treatment with interferon-alpha compared to vinblastine or medroxyprogesterone achieves a small improvement in survival. Response rates in patients treated with low dose IL-2 are similar to those achieved with a high dose bolus schedule but whether the responses are as durable is being addressed in an ongoing randomized trial. A randomized trial of interferon-alpha plus IL-2 compared to monotherapy with either agent showed increased toxicity but no improvement in survival. In 3 randomized trials no survival benefit was associated with adjuvant interferon-alpha therapy following complete resection of locally advanced renal cell carcinoma. CONCLUSIONS: Despite extensive evaluation of many different treatment modalities, metastatic renal cell carcinoma remains highly resistant to systemic therapy. A few patients exhibit complete or partial responses to interferon and/or IL-2 but most do not respond, and there are few long-term survivors. Preclinical research, and clinical evaluation of new agents and treatment programs to identify improved antitumor activity against metastases remain the highest priorities in this refractory disease.

Carcinoma, Renal Cell↗
PubMed1994

Adjuvant systemic therapy and survival after breast cancer.

BACKGROUND AND METHODS: We examined the effect of adjuvant systemic therapy on survival after breast cancer among the residents of the Canadian province of British Columbia. Data on survival were collected for all women in whom breast cancer was diagnosed in British Columbia during each of three calendar years chosen to represent different province-wide treatment recommendations: 1974, when no adjuvant systemic therapy was recommended; 1980, when adjuvant chemotherapy was recommended only for premenopausal women with node-positive disease; and 1984, when adjuvant chemotherapy was also recommended for premenopausal women with node-negative disease and lymphatic, vascular, or neural invasion and tamoxifen was recommended for postmenopausal women with involved lymph nodes or lymphatic, vascular, or neural invasion unless their tumors were negative for estrogen receptors. RESULTS: For women less than 50 years of age, disease-specific survival at seven years (i.e., with censoring of data on women who died from causes other than breast cancer) improved from 65.2 to 76.3 percent between 1974 and 1984 (P = 0.008), and overall survival improved from 64.8 to 74.6 percent (P = 0.02). For women from 50 through 89 years of age, disease-specific survival at seven years improved from 62.5 to 70.4 percent between 1980 and 1984 (P = 0.001), and overall survival improved from 53.9 to 58.3 percent (P = 0.05). The timing of the improvements in survival correlated with the introduction of adjuvant systemic therapy in each group. CONCLUSIONS: Survival among women with breast cancer improved significantly in a geographically defined population during the period when adjuvant systemic therapy became widely used.

Adult↗
PubMed2000

Primary systemic therapy in operable breast cancer.

PURPOSE: Laboratory studies suggest that primary systemic therapy (PST) could improve control of micrometastatic disease and impact on overall survival (OS). This article examines the rationale for and preclinical and clinical data of PST in operable breast cancer and the potential role of intermediate biomarkers as predictive and/or prognostic factors for response and survival. DESIGN AND METHOD: We conducted an extensive literative review (including MEDLINE) on preclinical studies, single-arm feasibility studies, large randomized single- and multi-institutional trials, and laboratory correlate studies of PST in breast cancer. RESULTS: Small trials in locally advanced disease showed high initial rates of response and local control. Six randomized clinical trials (RCTs) of PST for palpable, operable breast cancer have been reported since 1991 (from 204 to 1,523 patients each). These data clearly show a small but significant (less than 10%) absolute increase in the use of breast-conservation treatment (BCT) with similar rates of local control. Although one study showed better disease-free survival (DFS) and another showed better OS, most studies did not show any survival advantage of primary versus adjuvant systemic therapy. Thus far, pathologic complete response seems to be the best predictor of survival, but clinical response assessment correlates poorly with pathologic response. Pilot studies demonstrated feasibility of procuring tissue at diagnosis and after treatment for assays of potential intermediate biomarkers. Initial data suggest a potential correlation between markers of proliferation and apoptosis and in vivo chemotherapy sensitivity. CONCLUSION: Thus far, RCTs of PST versus standard adjuvant therapy have not shown any clear benefit for DFS or OS in early breast cancer. Ongoing trials should determine if specific subsets of patients at risk would benefit from additional systemic therapy and the potential role of intermediate biomarkers in identifying such women. Although PST results in a small increase in the rate of BCT with similar rates of local control, current PST strategies should not replace standard adjuvant approaches. Rather, they represent an acceptable alternative to women with palpable, operable tumors and an excellent arena for clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗