THE ASSESSMENT OF RESPONSE TO THERAPY OF BONE METASTASES IN BREAST CANCER

Serial bone scans, x-rays and records of bone pain were reviewed in order to determine the relative contributions of these parameters in the assessment of response of bone metastases to treatment. Twenty-seven patients with abnormal bone scans due to metastatic breast cancer were studied. Ten of the patients showed an early temporary flare on bone scan including five with apparent new lesions. Confirmation that such new lesions did not denote progressive disease was provided by subsequent improvement in symptoms and reduction in intensity and number of lesions on a follow-up bone scan, without any change in systemic therapy. Serial x-rays were found to be unreliable as a sole method for assessing response to therapy or disease progression, as in only seven of the 27 patients could a definitive radiological assessment of response be made. In only one patient did x-rays improve the accuracy of the scan by distinguishing between a healing flare and progressive disease. In contrast, this distinction was made in seven of the 10 patients on the basis of improvement in bone pain at the time of the flare. The other 3 patients had no bone pain prior to therapy or at the time of the flare. Tentative response criteria incorporating bone scan, x-ray and symptoms are suggested. The criteria incorporate recognition of the fact that new lesions appearing on a bone scan within six months of initiation of therapy may comprise part of a healing flare response.     

老年晚期乳腺癌新辅助化疗后再手术的临床研究

目的 探讨老年晚期乳腺癌经新辅助化疗后的临床效果。方法对23例老年晚期乳腺癌患者行新辅助化疗．手术前采用TA方案化疗2—3个疗程,再行手术治疗。结果 临床观察完全缓解（CR）0例,部分缓解（PR）8例,轻度缓解（MR）11例,无变化（NC）4例,总有效率为82．6％。病理检查可见肿瘤细胞有不同程度变性坏死,间质纤维组织增多,炎性细胞浸润。结论 新辅助化疗能大量杀伤肿瘤细胞,可使肿瘤缩小,降低临床分期,为手术创造有利条件,从而改善预后。     

HYPERTROPHIC PULMONARY OSTEOARTHROPATHY: RESPONSE TO CHEMOTHERAPY WITHOUT DOCUMENTED TUMOUR RESPONSE

Abstract: A case is reported of severe hypertrophic pulmonary osteoarthropathy associated with bronchogenic carcinoma which successfully responded to chemotherapy, despite the fact there was no objective response in the primary lesion. Previous treatment and responses are briefly reviewed. The method or methods by which chemotherapy may alleviate HPOA in the absence of response to the primary lesion are discussed. The marked discrepancy between progression of the HPOA and progression of the clubbing is noted. The fact that HPOA is potentially treatable despite the prognosis of the primary is emphasised.     

USEFUL ENDOSCOPIC ULTRASONOGRAPHY TO ASSESS THE EFFICACY OF NEOADJUVANT THERAPY FOR ADVANCED ESOPHAGEAL CARCINOMA: BASED ON THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS

Objective: The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods: Sixty‐two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD‐SD (progressive disease‐stable disease) was defined as < 30% reduction of tumor thickness on EUS, PR (partial response) as ≥ 30% reduction of tumor thickness, and CR (complete response) as no detectable tumor (100%). Results: The percent reduction of the thickness of Grade 0–1, Grade 2 and Grade 3 tumor was 11.5 ± 21.0%, 48.2 ± 17.0% and 74.9 ± 21.1%, respectively. There were significant differences in the extent of reduction among the three groups. Based on the RECIST, 80% of Grade 0–1 cases, 91% of Grade 2 cases and 22% of Grade 3 cases were PD‐SD, PR, and CR according to EUS, respectively. EUS correctly identified 80% of non‐responders and 94% of responders. Conclusions: The percentage reduction of tumor thickness on EUS closely reflected the pathological evaluation. EUS evaluation based on the RECIST seems to be useful for monitoring neoadjuvant therapy in patients with esophageal carcinoma.     

Breast cancer: Current and future endocrine therapies

Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones.     

INTESTINAL DOPAMINERGIC ACTIVITY IN OBESE AND LEAN ZUCKER RATS: RESPONSE TO HIGH SALT INTAKE

The present study examined intestinal dopaminergic activity and its response to high salt (HS, 1% NaCl over a period of 24 hours) intake in obese (OZR) and lean Zucker rats (LZR). The basal Na⁺,K⁺-ATPase activity (nmol Pi/mg protein/min) in the jejunum of OZR was higher than in LZR on normal salt (NS) (OZR-NS=111.3±6.0 vs. LZR-NS=88.0±8.3). With the increase in salt intake, the basal Na⁺,K⁺-ATPase activity significantly increased in both animals (OZR-HS=145.9±11.8; LZR-HS=108.8±6.7). SKF 38393 (10?nM), a specific D₁-like dopamine receptor agonist, inhibited the jejunal Na⁺,K⁺-ATPase activity in OZR on HS intake, but failed to inhibit enzyme activity in OZR on NS intake and LZR on NS and HS intakes. The aromatic L-amino acid decarboxylase (AADC) activity in OZR was lower than in LZR on NS intake. The HS intake increased AADC activity in OZR, but not in LZR. During the NS intake the jejunal monoamine oxidase (MAO) activity in OZR was similar to that in LZR. The HS intake significantly decreased MAO activity in both OZR and LZR. The jejunal COMT activity in OZR was higher than in LZR on NS intake. The HS intake reduced COMT activity in OZR but not LZR. It is concluded that inhibition of jejunal Na⁺,K⁺-ATPase activity through D₁ dopamine receptors is dependent on salt intake in OZR, whereas in LZR, the enzyme failed to respond to the activation of D₁ dopamine receptors irrespective of their salt intake.     

A,B, H,and Lewis-a and Lewis-b blood group antigens in human breast cancer: Correlation with steroid hormone receptor and disease status

Estrogen (ER) and progesterone (PR) hormone receptor status and levels were correlated with blood group antigen (A, B, H, Lewis-a and Lewis-b) expression in 48 cases of human breast cancer. Reduced expression of all the blood group antigens was observed with statistically significant reductions for H, Lewis-a and Lewis-b (P<0.05). The proportions of ER- and PR-positive breast cancers staining for Lewis-b were greater than in hormone-receptor-negative cancers but the differences were not significant. The loss of Lewis-b antigen in breast cancer increased with tumor grade but did not correlate with axillary lymph node metastases. Loss of Lewis-b antigen is probably not a predictor of local recurrence and survival in the short period of observation. We conclude that the loss of H, Lewis-a and especially, Lewis-b in breast cancer reflects the invasiveness of breast cancer and that Lewis-a and b expression is probably only marginally and not significantly affected by steroid hormone receptor status and levels.     

Care of the Cancer Survivor: Metabolic Syndrome after Hormone-Modifying Therapy

Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies might increase patients' risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones; thus, treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardiovascular disease, and insulin resistance. Anti-estrogen therapy in women with breast cancer can affect lipid profiles, cardiovascular risk, and liver function. As the number of cancer survivors continues to grow, treating physicians must be aware of the potential risks facing patients who have been treated with either androgen suppression therapy or anti-estrogen therapy so that early diagnosis and intervention can be achieved.     

Counting the costs of treatment: the reproductive and gynaecological consequences of adjuvant therapy in young women with breast cancer

Abstract
As the mortality rate from breast cancer decreases, the issues facing breast cancer survivors are becoming increasingly important. Survivors of all ages may face physical and psychosocial consequences of their diag­nosis and treatments. However, the long-term fertility and menopause-related side-effects of adjuvant therapy uniquely affect younger premenopausal breast cancer survivors. This article provides an evidence-based overview of the reproductive and gynaecological impact of breast cancer therapy for premenopausal women diagnosed with breast cancer. The physical and psychosocial implications of premature menopause are presented. Strategies for preserving fertility in selected patients are also discussed. Recent clinical trials strongly indicate that premenopausal women with oestrogen receptor positive tumours should receive endocrine therapy. The increased use of endocrine therapies in younger women raises important questions regarding patient information needs and treatment decision-making. (Intern Med J 2001; 31: 372−379)     

Fatigue in patients with adjuvant radiation therapy for breast cancer: long-term follow-up

Purpose The aim of this study was to evaluate fatigue 2.5 years after adjuvant radiation therapy (RT) in patients with localized breast cancer and to assess its relation to pre- and immediate post-treatment fatigue values. The association of fatigue with psychological distress and functional impairment was analyzed as well as pretreatment predictors for chronic fatigue.Methods Of a set of 41 patients whose fatigue was evaluated during adjuvant radiation therapy, 38 patients alive and free of cancer at 2.5 years (t2) after RT were assessed in this study. Patients received the Fatigue Assessment Questionnaire (FAQ), a visual analog scale on fatigue intensity (VAS-F) as well as on cancer-related distress (VAS-D), the Hospital Anxiety and Depression Scale (HADS), and three questions of the Short-Form 36-Item Health Survey (SF-36) per mail. All 38 patients returned their questionnaires. The values were compared to pretreatment (t0) and immediate post-treatment levels (2 months after RT, t1).Results There was no significant difference between chronic fatigue levels at 2.5 years after RT and pretreatment values. When compared to immediate post-treatment levels the FAQ global score and the HADS anxiety score displayed a significant increase. Cancer-related distress correlated closely with fatigue scores. Patients with functional impairment had slightly higher fatigue values. Age or hormonal therapy were not associated with chronic fatigue levels. Pretreatment fatigue and pretreatment HADS anxiety and depression scores were good predictors of fatigue at 2.5 years after RT explaining 60% (FAQ) and 49% (VAS-F) of its variance.Conclusions Fatigue 2.5 years after RT did not increase above baseline levels before RT in conservatively operated breast cancer patients. Chronic fatigue correlated closely with psychological distress. Patients with pretreatment elevated fatigue, anxiety or depression levels are at risk for chronic fatigue.     

Increasing protection after tamoxifen: insights from the extended adjuvant aromatase inhibitor trials

For disease-free postmenopausal women with hormone-responsive breast cancer, a risk for relapse remains following 5 years of adjuvant therapy with tamoxifen. Additional therapy with tamoxifen beyond 5 years is not indicated due to a demonstrated lack of efficacy beyond this time frame. Thus, there is a need for other endocrine therapy options in the period beyond 5 years. The third-generation aromatase inhibitors (anastrozole, letrozole, and exemestane) have emerged as at least as effective and somewhat better tolerated alternatives to tamoxifen. Three trials were initiated to evaluate the efficacy and tolerability of aromatase inhibitors in the extended adjuvant setting. Among these, the large, double-blind, randomized, placebo-controlled MA.17 trial has already demonstrated a significant benefit of letrozole when compared with placebo on disease-free survival in postmenopausal women previously treated for 4.5–6 years with tamoxifen. A smaller open-label trial, the Austrian Breast and Colorectal Cancer Study Group 6a has reported a significant benefit for anastrozole on recurrence when used as extended adjuvant therapy when compared with no treatment, and similar results have been seen with extended adjuvant exemestane in the National Surgical Adjuvant Breast and Bowel Project B-33 trial. The results of these trials have important clinical implications for the future of extended adjuvant hormonal therapy for breast cancer. Dr. Rose has served on advisory boards for Roche, AstraZeneca, Novartis, Eli Lilly, and Bristol Meyers Squibb and has participated in Speaker’s Bureau for AstraZeneca and Novartis.     

Monitoring circulating epithelial tumour cells (CETC) to gauge therapy: in patients with disease progression after trastuzumab persisting CETC can be eliminated by combined lapatinib treatment

Background

In breast cancers, the gene for the growth factor receptor HER2 can be amplified leading to increased aggressiveness and metastasis formation. The monoclonal antibody trastuzumab prolongs relapse-free survival highly significantly but eventually many patients relapse.

Method

In this study, CETC were monitored using the Maintrac^® method during adjuvant trastuzumab treatment and during subsequent treatment with capecitabine/lapatinib.

Results

In one patient, trastuzumab led to marginal reduction in CETC with disease progress. The combination of capecitabine/lapatinib was preliminarily capable to eliminate all CETC, however, CETC reappeared. The second patient received adjuvant taxane together with trastuzumab and 1 year of further trastuzumab during which CETC increased. After stopping trastuzumab skin metastases occurred. Capecitabine/lapatinib led to complete CETC elimination with stable disease.

Conclusions

In patients with lack of CETC reduction in spite of trastuzumab treatment correlated with disease progression the combination of capecitabine/lapatinib highly efficiently led to rapid elimination of CETC warranting further monitoring during such studies.

     

ARGON PLASMA COAGULATION: IN VIVO TISSUE DAMAGE TO THE ESOPHAGUS AND STOMACH AND CLINICAL EFFICACY FOR EARLY ESOPHAGEAL AND GASTRIC CANCER

Background: Argon plasma coagulation (APC) has been proven to be safe in vitro, and has been widely introduced to therapeutic endoscopy. We evaluated the thermal effects on esophageal or gastric wall in vivo, and its effectiveness as an adjunct to incomplete resection of early esophageal and gastric cancer after endoscopic mucosal resection (EMR). Methods: Thermal injuries were made using endoscopic APC irradiation in porcine esophagus and stomach under various conditions during general anesthesia, and depth of tissue damage was determined histopathologically. Patients with early gastric cancer (n = 24) and early esophageal cancer (n = 5) were treated with additional APC following microscopically incomplete EMR. APC was applied to coagulate the entire edge of EMR‐induced ulcer 1 week after resection at power/gas settings of 50 W and 1.5 L/min in the stomach, and 40 W and 1.5 L/min in the esophagus for less than 5 s at each point. Results: Depth of tissue damage was related to pulse duration and power output. At power/gas settings of 60 W and 2.0 L/min, thermal damage extended across the submucosal layer with 5‐s pulse duration in the stomach. Thermal damage with 5‐s pulse duration at power/gas settings of 40 W and 2.0 L/min extended to the muscularis propria in the esophagus. In the clinical study of additional APC therapy, the recurrence rate was 6.9% (two of 29 cases). Conclusion: To avoid perforation, we recommend an APC power setting of 40–60 W for less than 5 s in the stomach and a lower power setting with shorter duration in the esophagus. APC seems to reduce recurrence of esophageal or gastric cancer after incomplete EMR.     

Adjuvant ovarian suppression for premenopausal hormone receptor-positive breast cancer: A network meta-analysis

Background:Ovarian function suppressor (OFS) plus either tamoxifen (TAM) or aromatase inhibitor (AI) could improve the survival outcome for premenopausal hormone receptor-positive (HR+) breast cancer. However, the optimal OFS-based regimen and medication duration remain uncertain. This article aims to systematically evaluate the OFS-based adjuvant endocrine therapy for premenopausal breast cancer.Methods:We searched several public databases from January 1980 to November 2020. A random model was adopted in this meta-analysis. We used the hazard ratio (HR) with a 95% confidence interval (CI) for the statistical analysis of efficacy. The primary outcome measures included overall survival and disease-free survival.Results:A total of 32 articles with 37,224 cases were included in this network meta-analysis. OFS+TAM improved 5-year disease-free survival (HR –0.09, 95% CI –0.16 to –0.01) and 5-year overall survival (HR –0.18, 95% CI –0.33 to –0.03) compared with TAM monotherapy. For OFS+AI, although the 5-year disease-free survival was improved (HR –0.18, 95% CI –0.29 to –0.08), the 5-year overall survival was not improved (HR –0.13, 95% CI –0.43 to 0.18). In subgroup analysis, both OFS+AI and OFS+TAM showed a protective effect in stage I–III patients compared with stage I–II patients. For the course of therapy, OFS+TAM for 2-years could achieve clinical benefit and the best course of therapy of OFS+AI still waits for further study.Conclusions:OFS+TAM might be a better option than OFS+AI for premenopausal intensive adjuvant endocrine therapy. Stage III patients are more suitable for the OFS-based therapy. For the medication duration, the 2-years course of OFS+TAM could be effective. This analysis provides helpful information for selecting therapeutic regimen in intensive adjuvant endocrine therapy and identifying the target population.     

Palliative hormone therapy, low-dose chemotherapy, and bisphosphonate in breast cancer patients with bone marrow involvement and pancytopenia: report of a pilot experience

Background: The choice between supportive care or specific anticancer treatment for poor performance status (PS) breast cancer patients with multimetastatic disease and pancytopenia due to bone marrow involvement (BMI) often remains a clinical dilemma. Patients and methods: Five consecutive patients with poor PS (WHO 2 or 3) and severe pancytopenia due to BMI received concomitant hormone therapy, weekly low-dose chemotherapy (anthracycline or anthracenedione), and either oral clodronate or intravenous pamidronate. Hormone therapy was adjusted to the patients’ menopausal status and/or previous (adjuvant) therapy and consisted of either tamoxifen±LH-RH agonist or an aromatase inhibitor. Results: In the five treated patients, one treatment-unrelated death was observed in the early phase. Significant PS improvement, pain relief, and rapid normalization of the blood counts were observed in the remaining cases. No major toxic phenomenon was observed. No severe infection occurred, and red cell or platelet transfusions were not required after 1–4 months of treatment. Three patients showed objective tumor response. Overall survival ranged from 12 to 38 months. Conclusion: Due to its low aggressiveness and potentially high activity, this combined treatment should be preferred to supportive care alone. A significant survival gain can be obtained in patients who respond, even with initially poor PS.     

Quality of life over 5 years in women with breast cancer after breast-conserving therapy versus mastectomy: a population-based study

Purpose  Breast-conserving therapy (BCT) was developed to improve quality of life (QOL) in early stage breast cancer patients. Except for differences in body image, literature comparing the psychosocial sequelae of BCT with mastectomy is ambiguous and shows a lack of substantial benefits. However, knowledge regarding long term effects of treatment on QOL in breast cancer is very limited as most of the pertinent studies have been performed in the early post-operative period. Therefore we compared QOL in women with breast cancer undergoing BCT versus women undergoing mastectomy over a 5-year period following primary surgery. Methods  QOL was assessed at 1, 3, and 5 years after diagnosis in a population based cohort of 315 women with early stage breast cancer (UICC stage I-II) from Saarland (Germany) using the EORTC QLQ-C30 questionnaire and the breast cancer specific module BR23. Results  Breast-conserving therapy was performed in 226 women (72%). After control for potential confounding, women with BCT reported better physical and role functioning, were sexually more active and more satisfied with their body image already at 1 year after diagnosis (all P values < 0.05). Differences in overall QOL and social functioning were gradually increasing over time and became statistically significant only at 5 years. Conclusions  Whereas some, very specific benefits of BCT, such as a better body image, are already visible very timely after completion of therapy, benefits in broader measures such as psychosocial well-being and overall quality of life gradually increase over time and become fully apparent only in the long run.