Problems in evaluating response of primary breast cancer to systemic therapy

Summary The evaluation of the response of primary breast cancer to systemic therapy is difficult. Evaluable primary lesions may be assessed both by physical and by mammographic examination. In this study, response to therapy was evaluated after 4 cycles of CMF or CMF plus tamoxifen in 49 patients with locally advanced breast cancer entering a prospective randomized trial. In 35 patients response was evaluated by both physical examination and mammography. In some cases there was disagreement between physical examination and mammograhy in quantifying the magnitude of response. In 8 of 35 (22.9%), the overall response was overestimated by physical examination versus mammography, while in 3 of 35 (8.6%) the reverse was true. Taking into consideration different criteria in attributing the overall response, i.e. selecting physical examination only, mammography only, or the most favorable or the least favorable response between the two methods of assessment, the objective remission rates were 65.7%, 54.3%, 71.4% and 45.7%, respectively. The data suggest that both physical examination and mammography should be used in evaluating the response of primary breast cancer to a systemic treatment. Should these two methods yield contrasting results, the data obtained with each method should be reported. The best observed response may be employed in determining the overall response.     

钼靶X线检查在乳腺癌保乳手术中的应用

钼靶X线摄影诊断乳腺癌的诸多征象中,肿块和钙化是评价乳腺癌保乳手术的两个最常见也是最重要的指标.钼靶X线摄影的另一重要价值是对乳腺癌保乳治疗后的随访评价.在术后的X线征象中,钙化是乳腺癌保乳手术后残留或复发最重要的征象.     

Optical mammography: Diffuse optical imaging of breast cancer

Existing imaging modalities for breast cancer screening, diagnosis and therapy monitoring, namely X-ray mammography and magnetic resonance imaging, have been proven to have limitations. Diffuse optical imaging is a set of non-invasive imaging modalities that use near-infrared light, which can be an alternative, if not replacement, to those existing modalities. This review covers the background knowledge, recent clinical outcome, and future outlook of this newly emerging medical imaging modality.     

pS2 and response to adjuvant hormone therapy in primary breast cancer.

We reviewed 319 primary breast tumours for cytosolic pS2 content, with a median follow-up of 6 years. pS2 status correlated positively with oestradiol and progesterone receptors and negatively with Scarff, Bloom and Richardson grade. pS2 positivity was associated with longer overall survival, particularly in patients who received hormone therapy, in whom pS2 status was also predictive of the response to therapy.     

Letrozole as primary medical therapy for locally advanced and large operable breast cancer

Aims. To investigate the efficacy of letrozole 2.5mg and 10mg used as primary neoadjuvant therapy for patients with locally advanced and large operable breast cancer. Patients and Methods. Twenty-four postmenopausal patients with locally advanced or large operable breast cancer were treated in two consecutive series with letrozole 2.5mg (n=12) or letrozole 10mg (n=12). Response at three months was measured by change in tumor volume according to WHO criteria (partial response was defined as a reduction in tumor volume 65%). Tumor volumes were assessed clinically, by ultrasound and mammography, and pathologically. Results. All 24 patients were estrogen receptor-positive, were considered receptor-rich, and mean age was 77.6 years and 71.6 years in the letrozole 2.5mg and 10mg treatment groups, respectively. There were five complete clinical responses and seven partial clinical responses in the patients treated with 2.5mg letrozole, and nine partial responses and three patients with stable disease in patients treated with 10mg letrozole. Assessed by ultrasound and mammography, the 12 patients treated with 2.5mg had one complete response, nine partial responses and two with no change. In the 12 patients treated with 10mg letrozole, imaging gave eight partial responses and four with no change. One patient treated with the 2.5mg dose had a complete clinical and pathological response. There was no significant difference between the two doses in effect on tumor volume, and no recordable side effects associated with either dose. Conclusion. Letrozole used in a neoadjuvant setting is highly effective, producing clinically beneficial reductions in tumor volume allowing all patients to have breast conserving surgery, and has an acceptable safety profile.     

Molecular predictors of response to therapy for breast cancer

For several decades, measurements from tumor tissue biomarkers have been used to identify subsets of breast cancer patients that may benefit from specific therapies. Since the 1980s, estrogen receptor testing has been routinely performed on breast carcinoma samples to determine whether hormonal therapy is indicated. Today, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 testing to guide treatment decisions are standard of care. In recent years, multigene assays have been introduced to predict breast tumor behavior. In particular, the OncotypeDx and MammaPrint assays have been commercialized and are used in North America and Europe to guide clinical decisions. Others, including the Breast Cancer Index (BCI; bioTheranostics) and PAM50 (Expression Analysis, Inc), are gaining acceptance as validated assays with associated clinical outcomes. In addition, certain germ line genetic tests are now reported to predict response to specific treatments (e.g., BRCA1, 2, CYP2D6). The optimal use of these novel molecular assays is a challenge to the practicing oncologist. In this review, we will focus on the role of biomarkers that predict response to treatment of breast cancer patients and provide a framework for oncologists to understand and evaluate these tools for use in clinical practice.     

Primary medical therapy for operable breast cancer

Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy.With a median follow-up of 19 months (range 6–42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease.Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.     

Prediction of response to primary chemotherapy for operable breast cancer

The use of primary systemic cytotoxics leads to a high remission rate in patients with breast cancer. Response was identified as an important variable associated with survival. Thus, features which predict response, are potentially relevant for planning treatments and improving survival. Retrospectively, we investigated several histopathological features (expression of oestrogen and progesterone receptors, Mib1, bcl-2, c-erbB-2, and p53) prior to two programmes of either sequential preoperative chemotherapy (doxorubicin plus cyclophosphamide) and radiotherapy (Group A), or preoperative chemotherapy (5-fluorouracil, folinic acid and vinorelbine) alone (Group B) in patients with operable breast cancer. After three courses, patients with a partial or complete response were given a further three courses, which was followed for patients in Group A by radiotherapy 50 Gy plus a boost of 10 Gy. All patients were submitted to surgery after completion of preoperative treatment and pathology material from 73 patients (median age, 49 years, range, 30–70; performance status, 0–1; 68 T₂, 5 T₃) was obtained. The overall response rate according to radiological and clinical evaluation was 59% (68% for Group A and 49% for Group B). 12 of 14 patients with p53-positive tumours and 31 of 59 with p53-negative tumours responded (P=0.04). 6 of 7 patients with elevated c-erbB-2 had a response compared with 37 of 66 patients in the group with c-erbB-2 negative tumours (P=0.03). Mib1 expression decreased substantially (≥50%) in 25 patients during treatment, of whom 20 responded compared with 21 of 48 patients with a lower decrease (P=0.04). Response was observed in 28 of 37 patients with high baseline Mib1 (>20%) and in 15 of 36 patients in the low Mib1 group (P=0.05). Finally, 32 of 44 tumours with low expression of progesterone receptors responded compared with 11 of 29 tumours with high receptors expression (P=0.05). These markers might be useful for tailoring primary and postsurgical systemic treatments.     

三维适形放射治疗定位新技术在食管癌中的应用

目的：分析常规食管癌定位技术是否能够优化射野设计和提高CTV定位的准确率,探讨新定位技术在食管癌中的应用。方法：患者采用CT扫描前和扫描过程中口服一定量的阴性造影剂和阳性造影剂准确显示CTV。结果：运用该项定位技术可以相对准确测得肿块的长度和等中心,并且能够精确获得食管癌狭窄段位置、肿块大小及食管壁破坏程度,同时能清晰测得食管内、外侧壁。结论：该方法为精确放射治疗提供条件,提高了食管癌三维适形放疗的精确度。     

Prednisolone improves the response to primary endocrine treatment for advanced breast cancer

Two hundred and twenty patients with progressive advanced breast cancer were given primary endocrine treatment (PET) according to menstrual status. Pre-menopausal patients received ovarian irradiation (O) and post-menopausal tamoxifen 10 mg bd (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg bd (P). Similar results were observed in each menstrual subgroup. In 194 evaluable patients, the response to PET + P was 49% and to PET alone 30% (P less than 0.01). P increased the median duration of response from 9 to 14 months (P less than 0.002) and the median time to disease progression from 5 to 9 months (P less than 0.001). Response to P after O or T alone occurred in only 2/62 (3%). Median survival in patients randomised to receive P at the outset of PET was prolonged by 4 months (P less than 0.05). The addition of P significantly improves the response to O or T in the treatment of advanced breast cancer.     

Predictors of response to second-line endocrine therapy for breast cancer

This study reports on factors predicting response tosecond-line endocrine therapy in 250 patients with breastcancer for which they were assessable for responseby the International Union Against Cancer (UICC) criteria.Clinical details relating to first-line endocrine therapy wereavailable for all patients. We have not includedin this study patients who received first-line endocrinetherapy but did not or have not yetproceeded to second-line hormone therapy – e.g. diedfrom rapidly progressive disease, started chemotherapy for rapidlyprogressive disease, or remained in long-term remission onfirst-line endocrine therapy.One hundred and fifty nine patients (72%) achievedremission (objective response and static disease [OR +SD]) on first-line endocrine therapy with a medianduration of 19 months. For second-line endocrine therapythe remission rate was 53% (132/225) with amedian duration of 15 months. Tumour grade andoestrogen receptor status of the primary tumour wereshown to be independent predictors of response tosecond-line endocrine therapy while response to first-line endocrinetherapy was a predictor of the duration ofresponse to second-line endocrine therapy. In the sub-groupof patients who showed OR or SD toboth first and second-line therapies, there was nocorrelation between the time to progression (TTP) onfirst and second-line therapies.     

中央区乳腺癌的保乳治疗

目的 探讨中央区乳腺癌保乳治疗的可行性。方法 对157例肿瘤位于乳房中央区的Ⅰ～Ⅱ期及新辅助化疗后的Ⅲ期原发性乳腺癌患者,行局部扩大切除并腋窝淋巴结清扫手术,其中18例切除乳头乳晕区。手术前,93例接受2～6周期的新辅助化疗。手术后,全部患者的患乳接受放射治疗。结果 接受新辅助化疗的患者,临床有效率为87．1％（81／93）,术后病理学完全缓解率15．1％（14／93）。全部患者成功施行保乳治疗后,经随访6～53个月（中位随访23个月）,仅1例局部复发。保乳治疗后对患侧乳房外观的评价：88例优秀,48例良好,21例一般,总体优良率86．6％。结论 位于中央区的Ⅰ～Ⅱ期原发性乳腺癌患者,同样适合实施保乳治疗,近期疗效满意,远期效果有待长期随访观察。     

乳腺癌首期治疗后的远期并发症及处理

早期发现和综合治疗使乳腺癌患者的生存率明显提高,但经各种治疗后常遗留一些远期的并发症,导致长期生存患者生活质量降低,现综述这些并发症产生的原因及其处理措施.     

Tamoxifen therapy for primary breast cancer and risk of contralateral breast cancer.

BACKGROUND: Women diagnosed with breast cancer have a twofold to sixfold greater risk of developing contralateral breast cancer than women in the general population have of developing a first breast cancer. Tamoxifen therapy reduces this risk, but it is unclear if this benefit exists for both estrogen receptor (ER)-positive and ER-negative contralateral tumors. METHODS: Using data from a population-based tumor registry that collects information on the ER status of breast tumors, we followed 8981 women residing in western Washington State who were diagnosed with a primary unilateral invasive breast cancer during the period from 1990 through 1998 to identify cases of contralateral breast cancer. We restricted our analyses to women who were at least 50 years old and whose first breast cancer had a localized or regional stage; women who received adjuvant hormonal therapy but not chemotherapy (n = 4654) were classified as tamoxifen users, while those who received neither adjuvant hormonal therapy nor chemotherapy (n = 4327) were classified as nonusers of tamoxifen. By reviewing selected patient abstracts, we estimated that 94% of the subjects were classified correctly with respect to tamoxifen use. The risk of contralateral breast cancer associated with tamoxifen use was estimated with the use of Cox regression. All statistical tests were two-sided. RESULTS: Of the 89 tamoxifen users and 100 nonusers of tamoxifen diagnosed with contralateral breast cancer, 112 had ER-positive tumors, 20 had ER-negative tumors, and 57 had tumors with an ER status that was unknown or had not been determined by an immunohistochemical assay. The risk of developing an ER-positive and an ER-negative contralateral tumor among tamoxifen users was 0.8 (95% confidence interval [CI] = 0.5 to 1.1) and 4.9 (95% CI = 1.4 to 17.4), respectively, times that of nonusers of tamoxifen. This difference in risk by ER status was statistically significant (P<.0001). CONCLUSIONS: Tamoxifen use appears to decrease the risk of ER-positive contralateral breast tumors, but it appears to increase the risk of ER-negative contralateral tumors.     

Prediction of neoadjuvant chemotherapy response using diffuse optical spectroscopy in breast cancer

Purpose

Near-infrared diffuse optical spectroscopy (DOS) has been recently used to predict neoadjuvant chemotherapy response (NAC). In the present study, we explore the change in blood-oxygen content using DOS to predict NAC response against breast cancer.

Materials and methods

A total of 20 patients were enrolled and underwent DOS scan with blood-oxygen detection before each treatment cycle. The first DOS scan was performed before NAC treatment (pretreatment), and subsequent scans were performed after each NAC treatment circle. Changes in blood content and oxygen content by DOS were evaluated and compared with tumor size, and their changes were analyzed in response versus nonresponse group.

Results

Thirteen patients were classified into response and seven patients into nonresponse group. The tumor blood content value (?1.06 ± 0.43) and oxygen content value (0.48 ± 0.17) of DOS at pretreatment was significantly different from presurgery in response group (P < 0.05), but not in nonresponse group. In response group, the percentage change in blood content (median 91.19%) was significantly larger than tumor size (median 48.89%) (P = 0.0035), while in oxygen content (median 47.11%) is not (P = 0.2815). Comparing each cycle, the percentage change in blood content could distinguish responder from non-responder as early as after the first treatment cycle (19.1 versus 6.6%, P = 0.0265). Blood content percentage sensitivity was 76.9% and specificity was 85.7% (AUC 0.912), while oxygen content percentage sensitivity was 76.9% and specificity was 71.4% (AUC 0.797).

Conclusion

Both blood and oxygen content measured by DOS could be used to discriminate responder to the treatment versus non-responder. Among the two, percentage change of blood content was more precise and earlier than that of oxygen content to predicted breast tumor response. The percentage change in blood content could distinguish responder from non-responder after the first treatment cycle.

     

乳腺三维超声成像联合钼靶摄影在乳腺癌诊断中的应用价值

目的:研究乳腺三维超声成像联合钼靶摄影在乳腺癌诊断中的应用价值。方法:观察我院174例初步诊断为乳腺病变的患者,分别以乳腺三维超声、传统乳腺超声及钼靶摄影对患者病变情况予以评估,本组患者均经手术病理确认。结果:乳腺三维超声成像对乳腺癌诊断准确率优于钼靶摄影,但无统计学意义。三维超声联合钼靶摄影诊断乳腺癌敏感性、特异性及准确率均优于单独应用三维超声及钼靶摄影。结论:乳腺三维超声成像联合钼靶摄影可提高对乳腺病变良恶性鉴别的准确率,为早期确诊乳腺癌的可靠手段。     

Preoperative/neoadjuvant medical therapy for early breast cancer

Preoperative (neoadjuvant) medical therapy has emerged over the past decade as a new approach for the treatment of early breast cancer. Results show it has high activity, but survival is no better than with conventional adjuvant treatment. The need for mastectomy is reduced but not abolished; in some studies this effect is associated with a small increase in risk of local recurrence, but without any detriment to survival. Predictive factors for improved outcome include clinical response, and especially pathological complete remissions. However, persisting pathological axillary node involvement is associated with poor outcome. Biological changes in apoptosis or proliferation pathways may prove to be more sensitive surrogate markers than clinical or pathological responses for assessing treatment outcome. The main long-term aim of preoperative medical treatment must be to establish such surrogate predictive markers. This would lead to individualised treatment for each patient, and would allow much more rapid assessment of new drugs than is currently possible with adjuvant therapy trials.     

Prognostic significance of a combined clinicopathologic score for response to primary systemic therapy in locally advanced breast cancer

The response to chemotherapy is one of the best indicators of prognosis in locally advanced breast cancer (LABC). The pathologic response (pR) of 108 LABC patients was analysed and compared with their clinical response (cR). Our aim was to define a new combined clinicopathologic response score (cpR) and to explore its correlation with survival data. The 108 stage IIB to IIIB breast carcinomas were first treated with high-dose anthracycline-based chemotherapy. Standard criteria were used to assess cR. Pathologic analysis of surgical specimens allowed the definition of 5 types of pR. Three groups of combined clinicopathologic response were defined. Twenty-two patients (20%) had complete or almost complete pR. Most patients (88, 81%) had partial cR. This large group of partial cR was very heterogeneous, ranging from pR1 to pR5 and from cpR1 to cpR3. In univariate analysis, pR and cpR both strongly correlated with EFS. cR, pR and cpR all correlated with OS. Subgroups of incomplete pathologic responses were not prognostically different. In multivariate analysis, only cpR correlated strongly with both EFS and OS (p<0.002), identifying good (20%), intermediate (61%) and poor (19%) prognosis patients. In conclusion, in 108 stage IIB to IIIB breast cancer patients initially treated by high-dose chemotherapy, combined grading of clinical and pathologic responses in a single score allowed accurate prediction of outcome.