Adjuvant endocrine therapies for postmenopausal women with early breast cancer: standards and not

Hormonal manipulations have been used for more than 100 years for the treatment of metastatic breast cancer and after definition of the concept of micro-metastases also in the adjuvant setting. In the postmenopausal population, tamoxifen has played the most important role for almost four decades. Progestins or the first generation of aromatase inhibitors (AIs) were only marginally used in the adjuvant setting due to their prohibitive toxicity. The new generation of anti-estrogen compounds, the selective estrogen receptor down-regulators (SERDs) like fulvestrant have a higher affinity for the estrogen receptor than tamoxifen, but none of its agonist activities, and have shown promising clinical activity in the treatment of advanced breast cancer. The third generation of AIs investigated in six large trials has been reported to be superior to tamoxifen in terms of disease-free survival, but not in terms of survival. These trials will be discussed in terms of results in different subpopulations and of toxicity.     

Highest isotope count does not predict sentinel node positivity in all breast cancer patients

Background: Radioisotope mapping is an essential technical component of sentinel lymph node (SLN) biopsy, and most authors define isotope success by an arbitrary threshold SLN-to-background ratio. Few studies have examined the degree to which the relative level of SLN counts correlates with the presence of metastasis. Having removed the SLN with the highest counts, how far should the surgeon persist in removing additional SLN which contain much lower levels of isotope? Methods: We performed SLN biopsy, using both radioisotope and blue dye, in 2285 consecutive patients with stage I-II breast cancer. Successful isotope localization was defined as an ex vivo SLN-to-axillary background count ratio of at least 4:1, and enhanced pathologic analysis (serial sections and immunohistochemistry) was used throughout. Results: Among the 1566 patients with more than one SLN site identified, the SLN contained metastasis in 463 (30%). In 369 (80%) of these SLN-positive cases, the SLN with the highest count contained tumor, but in 94 (20%) it was benign. Among these 94: (1) the counts of the hottest benign SLN exceeded those of the histologically positive SLN by a ratio of at least 10:1 in 31% (29 of 94) of cases, (2) the counts of the positive SLN were < 4:1 those of the axillary background in 16% (15 of 94) of cases, and (3) blue dye failed to identify 27% of positive SLN. No optimum ratio of SLN-to-SLN or SLN-to-background counts identified the positive SLN in all cases. Conclusion:Although the SLN with the highest counts is positive in 80% of breast cancer patients with multiple SLN, neither a relatively high isotope count nor the presence of blue dye consistently predict SLN positivity in all breast cancer patients. For maximum accuracy, SLN biopsy requires (1) the removal of all nodes containing isotope regardless of the relative magnitude of counts, (2) the concurrent use of blue dye to salvage those procedures in which isotope fails, and (3) the removal of all clinically suspicious non-SLN.     

Egg retrieval with cryopreservation does not delay breast cancer treatment

BACKGROUND: Infertility is a concern to young women diagnosed with breast cancer. Advances in fertility technology have made it possible to bank fertilized embryos. METHODS: Twenty-three women, ages 27 to 40 years, underwent stimulation/oocyte retrieval before the start of adjuvant therapies. Time intervals between retrieval and therapeutic procedures were analyzed. RESULTS: The average stimulation to egg retrieval was 11.5 days (range 9-20 d). The average time interval from first evaluation to oocyte retrieval was 33.3 days (range 10-65 d). Overall, the mean time from definitive surgery to initiation of chemotherapy was 46.8 days (n = 20). For 6 patients referred by surgeons, the mean time from fertility consult to retrieval was 48.8 days (range 16-118 d), and from definitive surgery to initiation of chemotherapy was 45 days (range 15-93 d). CONCLUSIONS: Egg retrieval cryopreservation can be integrated with breast cancer work-up and surgical procedures. Early referrals to a fertility specialist by surgeons will help patients' safeguard future childbearing.     

Estrogen and combined estrogen-progestogen therapy in the menopause and breast cancer

Most of the data on menopausal hormone therapy (HT) and breast cancer risk available up to the mid-1990s were included in a collaborative reanalysis based on over 52,000 women with and 108,000 without breast cancer. HT increased the risk of breast cancer by about 2.3% per year of use. Subsequent studies have confirmed that breast cancer risk is elevated in current and recent (but not past) HT users and that the relative risk (RR) is higher for users of combined estrogen-progestin treatment than for users of estrogen only, and this higher RR is seen with various types of preparations and different routes of administration. With reference to intervention studies, information on combined HT derives from the Women's Health Initiative (WHI). After 7 years of follow-up, 166 breast cancer cases were recorded in the HT group, as against 124 in the placebo group, corresponding to a RR of 1.24. Data from two other, smaller, randomized studies are available. In a combined analysis of the three randomized trials, 205 cases of breast cancer were observed in the treated groups as against 154 in the placebo groups, corresponding to a pooled RR of 1.27. However, in the estrogen-only component of the WHI population, at 8 years of follow-up 94 cases were observed in the estrogen group, opposed to 124 in the placebo group (RR=0.77). The results recorded in the WHI and the Million Women Study do not confirm the suggestion that breast cancers in women using HT have a more favorable prognosis. HT has also been related to an increased risk of recurrent breast cancer.     

Mammographic appearance of ductal carcinoma in situ does not reliably predict histologic subtype

Histologic subtypes of ductal carcinoma in situ (DCIS) have been correlated with disease prognosis. There are conflicting reports on whether the grade of DCIS can be predicted by the morphology of calcifications seen on mammography. We undertook this study to determine whether the grade of DCIS can be reliably and accurately determined by mammography prior to excisional biopsy. Ninety consecutive cases of DCIS from 1993 to 1996 were identified, of which 75 cases had mammograms available for review. Any lesion with invasion was excluded. The mammogram showed only a mass in 10 of 75 cases, a mass and calcifications in 3 of 75 cases, and calcifications alone in 62 of 75 cases. Three board-certified radiologists with special expertise in mammography reviewed and categorized the mammographic findings as well, intermediate or poorly differentiated DCIS without knowledge of the histologic diagnosis. Histologic grading was performed without knowledge of the mammographic finding. Receiver operating curves (ROCs) were computed for each of the radiologists. For microcalcifications, the ROC comparisons of the radiologists' opinions of tumor grade and random chance were not significantly different. In those cases with available magnification views, the grade assessment did not change significantly. If only a mass was present on mammography, well-differentiated DCIS was the predominant histologic subtype. A histologic grade of DCIS cannot accurately be determined prospectively based on the mammographic appearance of microcalcifications. However, if only a mass is present, this is more likely to represent well-differentiated DCIS.     

甲状腺癌病人骨矿物质含量的研究

甲状腺癌病人在接受手术治疗和放射性碘清除残余甲状腺组织后，为了维持正常的甲状腺激素水平，必须接受激素替代治疗（HRT）。甲状腺激素能刺激骨骼的更新，加速骨质的形成和破坏，抑制剂量的甲状腺激素会引起骨矿物质的丢失。适当调整甲状腺癌病人的甲状腺激素替代治疗剂量，对于减少复发的可能和骨量的流失均十分重要。     

Trends in surgical treatment of breast cancer at Mayo Clinic 1980-2004

The study encompassed the time period January 1980 through December 2004. During this time 9485 women underwent mastectomy, 6847 women underwent breast conserving surgery (BCS) and 2477 women underwent breast radiotherapy (RT) for breast cancer. Linear regression modeling was used to quantify the rate of change in the proportion of women undergoing mastectomy during specific time periods. Chi-square tests were used to compare the proportion of women with a breast cancer less than 3 cm in size undergoing mastectomy the year prior to and the year after a specific event.There was a significant decrease in the number and proportion of mastectomies performed, an increase in the number of BCS procedures performed and an increase in the number of women undergoing breast RT around the times of (1) the employment of a young surgeon trained in BCS, (2) publication of the NIH Consensus Statement and (3) establishment of a multidisciplinary Breast Clinic.     

Factors associated with local breast cancer recurrence after lumpectomy alone: Postmenopausal patients

Background: We have been following a cohort of patients who underwent a lumpectomy without receiving adjuvant radiotherapy or adjuvant systemic therapy. We now report the experience of a postmenopausal subgroup. Methods: The postmenopausal subgroup included 244 patients accrued between 1977 and 1986 and followed up. The end point was ipsilateral local breast cancer recurrence. The factors studied were the patient’s age in years; tumor size (in mm); nodal status (N-, Nx, N+); estrogen and progesterone receptor status (<10, ≥10 fmol/mg protein); presence or absence of lymphovascular/perineural invasion; presence or absence, and type, of DCIS (none, non-comedo, comedo); percentage of DCIS; histological grade (1,2,3); and nuclear grade (1,2,3). Univariate analyses consisted of Kaplan-Meier plots and the Wilcoxon (Peto-Prentice) test statistic; the multivariate analyses were step-wise Cox and log-normal regressions. Results: The median follow-up of those patients still alive was 9.1 years, and the overall relapse rate was 24% (59/244). The univariate results indicated that the characteristics of smaller tumor size, negative nodes, positive ER status, and no lymphovascular or perineural invasion were associated with significantly (P<.05) lower relapse. From the multivariate analyses, the factors lymphovascular or perineural invasion, age, and amount of DCIS were all significantly associated with local relapse with both Cox and log-normal regressions. Additionally, there was weak evidence of an association between ER (P=.08 in the Cox regression and in the log-normal) and nodal status (P=.09 in the log-normal regression) with local relapse. We also are able to define a low-risk subgroup (N-, age ≥65, no comedo, ER positive, no emboli) with a crude 10-year local recurrence rate of 9%. Conclusion: With longer follow-up, and for postmenopausal patients, there continues to be support for the theory that local relapse is affected by the factors lymphovascular or perineural invasion, age, amount of DCIS, ER, and nodal status. A low risk subgroup has been identified. Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans.     

Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer

The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 ± 1.5 years (x ± SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 ± 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 ± 0.22 vs. −0.12 ± 0.25, +0.03 ± 0.19 vs. −0.54 ± 0.24, and +0.08 ± 0.14 vs. −0.02 ± 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 ± 0.04 vs. 0.40 ± 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (−2.1 ± 1.1 vs. +7.0 ± 3.3 μg/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 ± 2.5% vs. −0.3 ± 1.4%, and +8.1 ± 4.7 vs. −0.9 ±1.7, after 10.3 ± 0.4 and 17.3 ± 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.     

A UK national survey of breast surgeons on primary endocrine therapy of early operable breast cancer

Introduction

A significant proportion of elderly breast cancer patients in the UK have no surgical treatment recorded and appear to be treated with primary endocrine therapy (PET) only. Despite this, PET remains one of the poorly studied areas in breast cancer therapy and very little is known about the practice of PET in the UK.

Methods

A questionnaire comprising 14 questions relevant to PET was sent to 489 breast surgeons who were members of the UK Association of Breast Surgery and returned questionnaires were analysed.

Results

Overall, 228 questionnaires (47%) were returned. The vast majority (93%) of surgeons who responded use PET in early operable breast cancer in elderly women unfit for surgery or owing to patient preference but 7% would recommend PET to fit elderly patients. Most (76%) use letrozole. The percentage of elderly patients treated with PET varied from <10% to 70% between surgeons. The majority (77%) of respondents had not formally audited the outcome of their PET patients and over 70% underestimated the expected survival of an 80-year-old woman.

Conclusions

Most UK breast surgeons use PET in elderly patients with surgically resectable breast cancer. While most use it in unfit, frail patients, a minority would treat even fit elderly women with PET. Most surgeons have not formally audited the outcome of their patients treated with PET and underestimate the expected survival of elderly patients, which might have an impact on their decision to offer PET rather than surgery.     

microRNAs在乳腺癌及乳腺癌干细胞中的研究进展

microRNAs在乳腺癌形成和发展中发挥着重要的作用,其可能扮演着原癌基因、抑癌基因、肿瘤转移侵袭、凋亡、耐药调节者等角色。此外,越来越多的证据表明,miRNAs参与乳腺癌干细胞的增生、自我更新、分化及肿瘤形成。本文分别综述了microRNAs和乳腺癌、乳腺癌干细胞之间的关系及其用于肿瘤治疗的研究进展。     

Hormone conditioned cancer chemotherapy for recurrent breast cancer prolongs survival

Left suprarenal-inferior mesenteric venous shunt (Inokuchi) was prescribed for 80 patients with recurrent breast cancer and the efficacy of hormone coditioned cancer chemotherapy was assessed. The patients were separated into 3 groups according to the historical regimen of combined chemotherapy: Group I; surgical hormone therapy alone, Group II; surgery plus short term chemotherapy, and Group III; surgery plus long term chemotherapy. The 5 year survival rate of the responsive patients to the surgical hormone therapy was as high as 84.6 per cent in Group III, as compared to that of Groups I and II, 41.7 per cent and 16.7, respectively. Survival was not prolonged in non-responsive patients, regardless of the group. These findings indicate that surgical hormone therapy combined with postoperative long term cancer chemotherapy is a valid and effective method for treating recurrence of breast cancer.     

Interest in cavity shaving in breast conservative treatment does not depend on lumpectomy technique

In breast conserving surgery (BCS), the usefulness to perform systematic cavity shaving is actively debated. Some investigators argued that systematic cavity shaving could avoid surgical re-excision and make diagnosis of unexpected multifocality. Others argued that usefulness of cavity shaving depends on volumes of resection.In this study one hundred patients undergoing BCS with systematic cavity shaving were included. Margins less than 3 mm were considered to be insufficient. We tested clinico-pathological characteristics in order to identify predictive model of cavity margin shaving utility and we sought to determine if cavity margin shaving usefulness depends on volumes of resection. We showed that cavity shaving avoids the need for re-excision in 24% of cases as well as diagnosis of multifocality in 6% of cases. However, the clinical usefulness of cavity shaving was not related to the volumes of resection.     

Determinants of mastectomy in breast conservation therapy candidates

BACKGROUND: Although underused, breast conservation therapy (BCT) is an accepted method for treatment of noninvasive and early breast cancer. The purpose of this analysis was to identify factors associated with receiving mastectomy when eligible for BCT. METHODS: From a recent experience, 397 patients at the University of Texas M. D. Anderson Cancer Center presented with clinical stage 0, I, or II breast cancer. Demographics and tumor characteristics of patients who underwent BCT versus mastectomy were compared. RESULTS: Of 293 BCT candidates, 203 patients (69%) underwent BCT and 90 patients (31%) received a mastectomy. Of those 90 patients, 66 patients (73%) had documented concerns about receiving BCT. Multivariate analyses showed that widow status was a factor associated with receiving mastectomy at presentation (P = .04). CONCLUSIONS: The majority of BCT candidates with early stage breast cancer undergo BCT. In our study, widow status was a predictive factor of mastectomy in BCT candidates.     

Immediate reconstruction after mastectomy for breast cancer does not prolong the time to starting adjuvant chemotherapy

BACKGROUND: Immediate breast reconstruction is often performed after mastectomy for breast cancer. There has been concern that this will result in a delay in initiating chemotherapy and, as a consequence, may adversely impact survival. In this study we sought to determine whether immediate breast reconstruction affects the interval between surgery and adjuvant chemotherapy. METHODS: A single institution retrospective analysis was made using the institutional tumor registry and chart reviews. RESULTS: Forty-nine patients were identified who had undergone mastectomy with immediate reconstruction followed by adjuvant chemotherapy. They were compared with 308 patients undergoing mastectomy without reconstruction. Patients who underwent reconstruction were overall younger (46 versus 55, P <0.001), and had more advanced disease. The time to chemotherapy was significantly longer in the group receiving no reconstruction: 53 versus 41 days (P = 0.039). The type of reconstruction did not affect the time to chemotherapy. CONCLUSIONS: Immediate reconstruction after mastectomy does not increase the time to chemotherapy compared with mastectomy alone.     

Bone mineral density in old age: the influence of age at menarche and menopause

Being aware that age at menarche, age at menopause, and length of fertile period influence bone mineral density (BMD) in the early postmenopausal period, we have failed to find any earlier studies where such an influence on the axial skeleton has been studied in old age when the incidence of hip fracture starts to increase. A large cohort of women, all 75 years old (n = 1044) participated in the Malmö Osteoporosis Prospective Risk Assessment (OPRA) Study. The BMD of the lumbar spine and femoral neck was assessed by a dual-energy X-ray absorptiometry (DXA) technique. Age at menarche and at menopause was recalled with a questionnaire. Also, data on estrogen medication was collected. We found that, after excluding ever-users of potent estrogens (n = 49), there was a small but significant correlation of early menarcheal age with high BMD of the lumbar spine (r = –0.08; P = 0.017) and femoral neck (r = –0.10; P = 0.002) at age 75. Excluding the extremes (5% of the women) with very early or very late menarche, age at menarche no longer influenced the BMD in old age (r = –0.06; P = 0.113). Age at menopause had no influence on the BMD of the lumbar spine (r = 0.04; P = 0.246) or femoral neck (r = 0.00; P = 0.985), at age 75. The length of the fertile period did not influence BMD in old age. The influence of menarcheal or menopausal age on BMD at age 75 was not substantially altered after including body mass index (BMI) in a multiple regression model. Age at menarche or menopause seems to be of limited or no importance as a risk factor for osteoporosis when subjects are age 75 or older.     

Locally recurrent breast cancer after conservation therapy

BACKGROUND: Today, the majority of small invasive and noninvasive breast cancers are treated with breast conservation therapy (BCT). The incidence of local-regional recurrence (LRR) after BCT for stage 0, I, and II patients ranges between 5% and 22%. METHODS: A literature search for BCT, local recurrence, and regional recurrence was performed. Data from over 50 articles pertaining to the characteristics, risk factors, detection, management, and prognosis of these patients with LRR after BCT were collected and analyzed. RESULTS: Positive margins, high-grade ductal carcinoma in situ (DCIS), young age, and the absence of radiation therapy after BCT increase the risk for LRR. Prognosis at LRR is impacted by invasive versus noninvasive histology, size and stage, method of detection, and involvement of skin and/or axillary lymph nodes. The standard treatment is salvage mastectomy. CONCLUSIONS: The prognosis for LRR after BCT is favorable compared with patients with postmastectomy chest wall recurrence.     

乳腺癌内分泌治疗发展与未来

乳腺癌是激素依赖性肿瘤,内分泌药物的选择除了根据患者的年龄、病灶部位、手术到复发的间隔时间以及受体测定等因素外,还要根据不同药物的作用机制以及副反应而定。随着对内分泌治疗药物作用机制的深入研究和大规模临床研究的证实,激素受体阳性乳腺癌的内分泌治疗疗效将不断提高。     

难以扪及肿块的早期乳腺癌98例临床分析

目的：探讨难以扪及的早期乳腺癌的诊断与治疗。方法：对1992年2月～2005年10月收治的乳腺癌病例中，计有T0期98例，根据易感因素，结合彩超、钼靶、乳管造影、局部切除活检等法，进行诊断和治疗分析。结果：全组接受手术治疗并经病理组织学确定为Tis-TlbN0M0。的乳腺癌，多数为非浸润性或早期浸润性癌（84．6％）。全组的疗效佳，预后好。结论：重视T0期乳腺癌的临床某些细微变化及高危因素，不轻易放过常规检查中的每一可疑征象．是提高早期乳腺癌发现率的有效措施。