Chemoprevention for breast cancer

Despite the progress that has been made in breast cancer diagnosis and treatment, this disease is still a major health problem, being the most frequently diagnosed cancer and the first leading cause of cancer death among women both in developed and economically developing countries. In some developed countries incidence rate start to decrease from the end of last millennium and this can be explained, at least in part, by the decrease in hormone replacement therapy use by post-menopausal women. Chemoprevention has the potential to be an approach of utmost importance to reduce cancer burden at least among high-risk populations. Tamoxifen and raloxifene are both indicated for the prevention of breast cancer in women at high risk for the development of the disease, although raloxifene may have a more favorable adverse-effect profile, causing fewer uterine cancers and thromboembolic events. Aromatase inhibitors will most probably become an additional prevention treatment option in the near future, in view of the promising results observed in adjuvant trials and the interesting results of the very recently published first chemoprevention trial using an aromatase inhibitor.(2) Despite impressive results in most clinical trials performed to date, chemoprevention is still not widely used. Urgently needed are better molecular risk models to accurately identify high-risk subjects, new agents with a better risk/benefit ratio and validated biomarkers.     

Screening for breast cancer

Screening for breast cancer using the combination of physical examination of the breasts and mammography was effective in women age 50 or more in the HIP study. However, major questions remain, especially the benefit of screening women age 40-49, and the independent effect of mammography. Such questions can only be answered by large-scale randomized controlled trials, and trials to answer these questions are now underway in Canada (the NBSS) and Sweden. Only the NBSS, however, is attempting to replicate the HIP study in women age 40-49, and to evaluate the additional contribution of mammography to annual physical examination in women age 50-59. The Swedish studies are evaluating the effectiveness of mammography alone, while studies in Britain will help to evaluate breast self-examination (BSE) and biannual mammography with annual physical examination. Because much of the benefit in HIP could have derived from the physical examination, it is necessary to complete the present trials before population-based screening for breast cancer using mammography can be advocated. Trials are justifiable because the risk of mammographic screening seems likely to be negligible, and the use of the combination of annual mammography and physical examination to be cost-effective. In the meantime, there seems no immediate substitute on a population basis for efficient physical examination of the breasts by primary care physicians coupled with breast self-examination by the woman. Techniques such as ultrasound and diaphanography seem unlikely to supplant mammography in screening, and in any case, have to be evaluated in comparison with mammography.     

Tykerb for breast cancer

There are four members of the ErbB family: the epidermal growth factor(EGF)receptor(also called HER1 or EGFR), HER2, HER3 and HER4. Dimerization is the process whereby two HER receptor molecules associate to form a noncovalent complex. HER dimers are the active receptor forms required for transmission of external stimuli to the interior of the cell. HER dimerization occurs upon ligand binding and both HER homodimers and heterodimers can be formed in the process. However, HER2 appears to be the preferred dimerization partner of the other HER family members. Fifteen～20% of all breast cancers are HER2 positive and have a poor prognosis. Trastuzumab is an excellent, rationally-designed targeted cancer treatment. It is a recombinant, humanized, anti-HER2 monoclonal antibody that specifically binds to the extracellular area of HER2. However, the overall trastuzumab response rate is low, and the causes of trastuzumab resistance are poorly understood. Thus, there is a need for alternative anti-HER2 strategies for trastuzumab-resistant disease. Lapatinib is an orally administered small-molecule, reversible inhibitor of both EGFR and HER2 tyrosine kinase, and its activities include subsequent inhibition of its down- stream MAPK-ERK1/2, and the AKT signaling pathway. Lapatinib is more active when used in combination with capecitabine. For women with trastuzumab pre-treated HER2-positive breast cancer, Here, I will review the basics of EGFR and HER, and the treatment strategy for HER2-positive breast cancer with lapatinib.     

Screening for breast cancer

Strong evidence supports the value of breast cancer screening with mammography, and high-quality mammography screening can be considered a major public health achievement. As noted earlier in the discussion about the evaluation of service screening, the group of women who did not participate in mammographic screening in the decades after screening had been introduced had essentially unchanged or only minor improvements in mortality compared with the pattern before the introduction of screening, despite widespread use of adjuvant chemotherapy or hormonal therapy. Breast cancer should be treated in its preclinical phase if we are to save the lives of women with this disease, and a considerable body of evidence outlines best practices that, with broader adherence, would result in greater breast cancer mortality reductions than have been observed to date.     

Screening for breast cancer

This review will give a general overview of the impact of breast cancer, as well as breast cancer risk factors, identification of high-risk groups, screening modalities, and guidelines for screening average-risk and high-risk individuals, including a case discussion of the primary care provider’s approach to screening.     

Cryosurgery for breast cancer

As the majority of breast cancers present as small non-palpable lesions, alternatives for surgical lumpectomy come into consideration. Breast tumor ablation without surgical excision may be a less morbid procedure without sacrificing cancer control. Cryosurgery is one of several ablative options for the treatment of small unifocal breast cancer. The potential advantages include avoidance of a surgical procedure, less overall discomfort, improved cosmesis, quicker recovery and the prospect of overall cost benefits. Clinical experience in 29 patients is reviewed demonstrating effectiveness in properly chosen patients. A comparison of ablation methods is discussed. Finally, future research of the role of cryosurgery in the management of breast cancer is described.     

晚期乳腺癌及复发性乳腺癌的介入治疗

目的研究晚期乳腺癌及术后复发性乳腺癌的介入治疗方法及其临床意义。方法对24例患者先行患侧锁骨下动脉造影,确定病灶的供血动脉,然后超选择插管,根据病灶的大小及血供情况注入抗癌药物。结果乳腺癌原发灶、转移淋巴结及复发病灶,均有多支动脉供血,其中胸外侧动脉、胸背动脉及内乳动脉是最常见的供血动脉。介入治疗完全缓解率(CR)为16.7%(4/24),部分缓解率(PR)为62.5%(15/24),有效率为79.2%(19/24)。并使部分不可手术乳腺癌,介入治疗后可以手术治疗。毒副作用较轻。结论介入治疗可了解病灶的供血,是对晚期及术后复发性乳腺癌有效的治疗方法。     

Controversies in breast conservation treatment for breast cancer

Breast conservation treatment has become the standard treatment for early breast cancer patients, after the equivalence of mastectomy and breast conservation treatment was demonstrated in prospective, randomized trials and large retrospective studies. New questions, such as the feasibility of neoadjuvant chemotherapy in improving breast conserving rate, the appropriateness of breast conservation treatment in ductal carcinoma in situ, the effectiveness of radiation therapy in patients treated by breast conservation, and patient selection for breast conservation without radiation, are now being raised. Future work that needs to be done to answer these questions is discussed in this review.     

早期乳腺癌部分乳腺加速放疗

随着乳腺癌术后复发模式的研究进展,部分乳腺照射方法 成为乳腺癌放疗的热点.组织间插植、球囊近距离治疗、术中放疗及三维适形放疗和调强放疗等部分乳腺加速放疗已进入临床研究.其局部控制率和安全性与全乳腺照射比较相当,同时具有治疗周期短、方便患者等优势.部分乳腺加速放疗在部分患者有望代替全乳腺放疗,成为早期乳腺癌保乳术后放疗的标准治疗之一.

Abstract：

With a view to patterns of local recurrence after breast conserving surgery, whole breast irradiation(WBI) after surgery is controversial and partial-breast irradiation(PBI) came up. Many clinical trials related with accelerated partial-breast irradiation using a variety of radiotherapeutic techniques such as interstitial brachytherapy (IBT), MammoSite Radiation Therapy System, intraoperative radiotherapy(IORT), threedimensional conformal radiotherapy(3-DCRT)and intensity modulated radiation therapy(IMRT) in selected patients have been carried out. Accelerated partial-breast irradiation that provides faster, more convenient treat-ment demonstrates local control rate and safety comparable to that of whole breast irradiation. Partial breast irradiation may be an alternative way to whole breast radiotherapy and will be one of the standard treatments in women with early breast cancer seeking breast conservation.     

Adjuvant treatment for early breast cancer: the Ludwig breast cancer studies

The Ludwig Breast Cancer Study Group conducted four concomitant trials involving adjuvant chemotherapy and endocrine therapy. In Ludwig I, adjuvant combination chemotherapy was used with or without prednisone to treat premenopausal and perimenopausal women with metastases in 1-3 axillary lymph nodes. The impact of adding low-dose, continuous prednisone (7.5 mg/day) to an adjuvant, chemotherapy regimen of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was investigated in a randomized trial of 491 premenopausal and perimenopausal patients with operable breast cancer and metastases in 1-3 axillary lymph nodes. As a consequence of lower hematologic toxicity, a significantly higher dose of CMF could be administered with added prednisone (P less than 0.0001). However, at the 4-year median follow-up, no significant improvement was observed in disease-free survival (DFS) (73% vs. 77%; P = 0.35) or overall survival (OS) (both 86%; P = 0.73). Induced amenorrhea was associated with a longer DFS for younger patients, those who received lower CMF doses, and those with tumors that were estrogen receptor (ER) positive. In Ludwig III, adjuvant therapy was administered to younger postmenopausal women in a study of chemotherapy plus endocrine therapy versus endocrine therapy alone versus mastectomy alone. In this randomized trial of 463 postmenopausal women 65 years of age or younger with axillary node metastases, treatment with the combination of CMF plus low-dose prednisone and tamoxifen (CMFp + T), was compared to endocrine therapy alone (p + T) or to no further treatment after total mastectomy and axillary clearance. At a median follow-up of 4 years, the DFS was 61% for the CMFp + T group, compared with 48% for the p + T group (P = 0.01) and 31% for the observation group (P less than 0.0001). The 4-year OS rates were not statistically different (76%, 67%, and 68%, respectively; P = 0.30). Treatment with CMFp + T reduced local, regional, and distant metastases and was equally effective in improving DFS in patients with ER-positive or ER-negative tumors. In Ludwig II, chemotherapy was given with or without oophorectomy in premenopausal and perimenopausal patients with metastases in 4 or more axillary nodes.(ABSTRACT TRUNCATED AT 400 WORDS)     

三阴乳腺癌治疗研究进展

Triple-negative breast cancers (TNBCs) neither express estrogen receptor and progesterone receptor nor overexpress human epidermal growth factor receptor-2. Because of the special molecular features, triple-negative breast cancer is not either sensitive to endocrine therapy or targeted therapy of trastuzumab. There has not been standard treatment regimen for triple-negative breast cancer yet and chemotherapy has still been the chief therapy currently. However, with the great progress of oncology and molecular biology, the understanding of the natural history, pathophysiology and molecular features of this disease has been greatly improved, and a growing number of novel and effective therapies and discoveries of new biological targets for this phenotype of breast cancers have been reported, which provide new insights into therapeutic strategies for the women suffering from it.     

Endocrine therapy for breast cancer

In addition to ovarian ablation by means of surgery or irradiation, a wide variety of endocrine agents are now available for the management of breast cancer, in both the metastatic and adjuvant settings. Currently available endocrine agents include antiestrogens, progestational drugs, and aromatase inhibitors. Randomized trials and meta-analyses have greatly clarified the specific roles of the more established of these agents in both premenopausal and postmenopausal women. However, the exact combination and sequence of these drugs are still under investigation. The addition of the bisphosphonates has also helped improve the quality of life of patients with metastatic disease. Among new endocrine agents currently under development are the pure antiestrogens, selective estrogen receptor modulators (SERMs), and a group of drugs with effects intermediate between the two.     

Computed radiography for breast cancer

In order to evaluate the possibility of using computed radiographic mammography in mass surveys of the breast, we have retrospectively examined 71 breast cancer lesions in 71 patients using computed radiographic and conventional non-screen mammographies and have carried out comparative studies on tumor detection rate and calcification. A 95.8% detection rate was obtained for the tumor image (n 71) using computed radiography (CR) and one of 93.0% using non-screen techniques. Three lesions remained undetected by either study. A 100% detection rate was obtained for calcification associated with cancer (n 33) from each method. No significant differences in either detection rate or calcification were seen between the two images. On the other hand, the ability to recognize tumor images (n 66) was as follows; CR superior to non-screen radiography in 53 lesions (80.3%), equal in eight lesions (12.1%) and inferior in five lesions (7.6%). For the calcification images (n 18), CR was superior to non-screen radiography in all 18 lesions. Obviously, CR gives better results than non-screen radiography. Furthermore, an adequate image can be obtained using CR even although the X-ray dosage is only a twentieth of that required for non-screen radiography. It can therefore be applied not only to mass surveys for breast cancer but also to routine clinical diagnoses.     

Radiotherapy for recurrent breast cancer

Evidence has shown that the right choice of tissue volume to be irradiated is much more important for better therapeutic effect than focal dose variation within 50-80 Gy. No relationship between efficacy of postoperative recurrence treatment, on the one hand, and multiplicity of lesions, recurrence ulceration or additional excision of relapsing node, on the other was established. However, lowered radiosensitivity and relatively very high likelihood of tumor dissemination were typical of tumors larger than 3 cm. Radiotherapy for primary tumor did not affect recurrence radiosensitivity, slowed down its development but might promote acceleration of its dissemination.