Considerations for the Treatment of Young Patients with Breast Cancer

Breast cancer in the young patient, generally defined as younger than 40 years, is a rare but important problem. In the US, over 24,000 women under age 45 are diagnosed with breast cancer each year and nearly 2,500 young women die annually of the disease. This review is intended to address issues specific to caring for the young breast cancer patient including diagnosis, genetic counseling, tumor biology, surgery, and potential for development of contralateral breast cancer. Additionally, there are psychosocial considerations unique to this age group which should be addressed as part of a comprehensive, multi‐disciplinary team approach including discussions about fertility, sexual function, behavioral health, and quality of life.     

Incorporating Genomic and Genetic Testing into the Treatment of Metastatic Luminal Breast Cancer

BackgroundTreatment of patients with luminal metastatic breast cancer (MBC) has become even more complex over the last few years as molecular profiling has begun to alter disease management. It is well accepted that MBC is not curable but is treatable. Today we are able to prolong progression-free survival and partly overall survival with targeted and more individual treatment strategies adjusted according to the molecular subtype.SummaryGenetic and genomic testing has become therapeutically relevant in luminal MBC and is therefore an integral component within the treatment spectrum. By now, germline testing of BRCA1 and BRCA2 and somatic testing for PIK3CA mutations are inevitable elements in disease management and the current state of the art in luminal MBC patients. Furthermore, testing of ESR1 resistance mutation, ERBB2 mutation, microsatellite instability, and neurotrophic tyrosine receptor kinase (NTRK) gene fusion (mainly in secretory breast cancer) has recently gained increasing attention. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities. The following review summarizes current developments in genetic and genomic testing in luminal MBC.Key MessagesIn luminal MBC genomics have become an integral component within the spectrum of oncological treatment establishing novel therapeutic facilities. Further developments in treatment personalization adjusted according to the molecular subtype should become increasingly important in order to enhance the progress of de-escalation of chemotherapy in luminal MBC. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities.     

Trastuzumab,Pertuzumab, and Docetaxel as the First Line for HER-2-Positive Metastatic Breast Cancer among Arabs

IntroductionHuman epidermal growth factor receptor 2 (HER-2) targeted therapy regimens can improve tumor response in HER-2-positive metastatic breast cancer (MBC), with overall survival benefits.ObjectiveWe evaluated the efficacy of dual HER-2 blockade combined with chemotherapy for HER-2-positive MBC patients as a first-line therapy in our patient population.Patients and MethodsWe identified 75 patients at King Faisal Specialist Hospital and Research Center that received trastuzumab, pertuzumab, and docetaxel as a first-line therapy in HER-2 positive MBC in 2013–2016.ResultsMedian age at diagnosis was 45 years; 54.7% were estrogen receptor (ER)-positive. 10% of patients presented with only bone metastasis. The median follow-up time was 36 months with an objective response rate of 74.7% (complete response [CR] 18.7%; partial response [PR] 56%). The 5-year progression-free survival (PFS) and overall survival (OS) were 21% and 71.9% respectively, with a median PFS of 36 months (95% confidence interval [CI] 23.6–48.4). The 5-year OS for ER-negative and ER-positive patients was 93.9% and 59.4% respectively (p = 0.189); 23 patients experienced grade 1/2 toxicity and 2 patients had grade 3/4 toxicity. In terms of OS and PFS, the site of metastasis did not make any significant difference.ConclusionsFirst line pertuzumab, trastuzumab, and docetaxel for HER-2-positive MBC patients was found to be an effective and safe therapy in the Saudi population. This finding was consistent with the results seen in the CLEOPATRA trials.     

Weekly nab-Paclitaxel in Metastatic Breast Cancer - Summary and Results of an Expert Panel Discussion

Taxanes are regarded as the most effective single agents in the treatment of metastatic breast cancer (MBC). For conventional taxanes, crucial toxicities and impairments in clinical efficacy are related to solvents necessary because of the agents' hydrophobicity. The mandatory premedication with corticosteroids causes additional side effects. Nab-paclitaxel is a solvent-free colloidal suspension of paclitaxel and human serum albumin that exploits the physiological transport properties of albumin. It is registered as monotherapy with a recommended dose of 260 mg/m(2) every 3 weeks for the treatment of patients with MBC, who have failed a first-line treatment of metastatic disease and for whom a standard anthracycline treatment is not indicated. Clinical evidence is available for the registered 3-weekly administration and for alternative weekly schedules in first and further lines of therapy of patients with MBC. During an advisory board meeting, a group of 8 German breast cancer experts reviewed the clinical data of nab-paclitaxel in MBC and discussed how nab-paclitaxel could be used in clinical practice on the basis of the current data.     

Multicenter Phase II Study with Weekly Bendamustine and Paclitaxel as First- or Later-Line Therapy in Patients with Metastatic Breast Cancer: RiTa II Trial

The combination of bendamustine (B) and paclitaxel (P) as anthracycline-free treatment option in patients with advanced breast cancer has been evaluated in the previous RiTa I trial. The regimen of weekly B 70 mg/m(2) and P 90 mg/m(2) with a pause every 4th week was established as an effective regimen with low toxicity. The aim of the present RiTa II study was to investigate the potential of BP as anthracycline-free combination therapy. The primary objective was to determine the progression-free survival (PFS); secondary endpoints were safety, tolerability, overall response rate (ORR) and overall survival (OS). 26 patients were available, 15 received BP as first-line, 11 as beyond first-line treatment. 27% patients had triple-negative breast cancer (TNBC). Median PFS and OS were 7.3 months (95% confidence interval (CI): 5.5-10.9) and 14.9 months (95% CI: 9.9-22.9), respectively. The 1-year PFS rate was 20.3% and the 1-year OS rate 71.2%. The ORR was 42.3%, including 4 complete and 7 partial remissions. TNBC patients reached an ORR of 71.4%. Anthracycline-pretreated patients showed an ORR of 43.8%, confirming bendamustine's lack of cross-resistance to anthracycline agents. BP represents a favorable option with moderate toxicity in pretreated metastatic breast cancer and offers a possibility for application in anthracycline-pretreated and TNBC patients.     

Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period

IntroductionThe purpose of this study was to study the efficacy of subsequent treatment lines for metastatic breast cancer (MBC), as well as the association between radiologic objective response rate (ORR) and overall survival (OS).MethodsIn this retrospective study, consecutive patients treated for MBC in two centers in Greece from January 1, 1992, to December 31, 2016, were identified and clinicopathologic data regarding tumor characteristics and administered treatments were collected. The efficacy per treatment line in terms of ORR, progression-free survival (PFS) and OS, as well as the prognostic value of ORR at first line were investigated.ResultsA total of 977 patients with MBC were identified; 950 received any treatment. At first line, ORR was 43.5%, PFS 11.4 months (95% CI 10.4–12.4), and median OS 52.4 months (95% CI 47.7–57.1). Lower ORR and shorter PFS were observed with each subsequent line. Median OS was significantly longer for patients that had an objective response at first line, 61.9 months (95% CI 51.1–69.7) for responders versus 41.3 months (95% CI 44.1–63.3) for nonresponders (p < 0.001). In multivariable analysis, failure to achieve an objective response was an independent predictor of poor survival (hazard ratio 1.70, 95% CI 1.34–2.15, p < 0.001).ConclusionLate treatment lines for MBC seem to have limited efficacy, while response to first-line therapy is associated with long-term survival. The latter should be considered in the treatment strategy of patients with MBC.     

Treatment of Recurrent Breast Cancer Following Breast Conserving Surgery

Patients with isolated ipsilateral breast cancer recurrence face completion mastectomy in the majority of cases. Selected patients may derive good outcomes from repeat breast conservation surgery and indeed repeat irradiation may be employed using one of many different modalities. Tumor biology rather than salvage surgery method is likely to influence outcome. Patients with isolated breast tumor recurrence are treated in the majority of cases with completion mastectomy, when for selected patients there exists little evidence that more radical surgery provides better outcomes in terms of further recurrence and overall survival, than repeated breast conserving surgery. Literature search identifying articles addressing the issue of repeat breast conserving surgery for ipsilateral breast tumor recurrence, and repeat radiotherapy (search terms include: repeat breast conserving surgery, salvage mastectomy, salvage breast conserving surgery, salvage radiotherapy, reirradiation). Thirty‐five articles discussed the outcomes of repeat breast conserving surgery versus salvage mastectomy, methods of repeat breast irradiation, repeat sentinel lymph node biopsy and related factors. Repeat breast conserving surgery may represent a safe and feasible treatment method for isolated ipsilateral breast tumor recurrence.     

Impact of body mass index on the efficacy of endocrine therapy in patients with metastatic breast cancer - A retrospective two-center cohort study

BakgroundThe aim of this study was to investigate the impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal women with metastatic hormone receptor breast cancer (HR+BC) as well as to identify if the potential difference in efficacy was associated with Fulvestrant only or both aromatase inhibitors (AIs) and Fulvestrant.MethodsA consecutive cohort of postmenopausal women with HR+metastatic breast cancer that have received endocrine therapy including Fulvestrant as a metastatic treatment strategy at the Departments of Oncology in Eskilstuna and Uppsala, Sweden, between 2008 and 2016 were identified. The primary outcome of the study was time to disease progression (TTP) during the treatment with Fulvestrant in overweight and obese women compared to patient with normal BMI.ResultsIn total, 173 patients were enrolled in the study cohort, amongst these, 141 patients received both Fulvestrant and AIs and 32 received only Fulvestrant. No statistical significant association was observed between the three BMI categories and TTP, during Fulvestrant treatment (p = 0.136). The rates of objective response and clinical benefit due to Fulvestrant were similar among patients with normal weight, overweight and obesity, respectively.ConclusionsNo difference in treatment efficacy was seen between normal, overweight and obese women with metastatic HR+BC, when treated with Fulvestrant. Until further research with prospective studies is available, there is no evidence to support any modification in how Fulvestrant treatment is used in patients with metastatic breast cancer in regard to BMI.     

Efficacy of Breast Conservation Therapy in Early Stage Bilateral Breast Cancer

The purpose of this study was to evaluate the outcome of patients with bilateral breast cancer as compared to unilateral breast cancer treated with breast conservation therapy. Sixty patients with bilateral breast cancer (BBC) and 1,080 unilateral breast cancer (UBC) patients treated with breast conservation therapy from 1977 to 1994 were analyzed for outcome. Of the 60 bilateral patients, 44 were metachronous bilateral breast cancer patients (MBBC) and 16 were synchronous bilateral breast cancer patients (SBBC). The majority of patients received lumpectomy, axillary node dissection, and localized radiation therapy. Median tumor size was 1.4 cm for BBC and 1.5 cm for UBC patients. Median total dose to the tumor bed was 60 Gy for both unilateral and bilateral patients. Of the 44 MBBC patients, 14 received breast conservation for both the first and second lesions, while 30 received breast conservation for only the second metachronous lesion. Thus 58 lesions in 44 patients were treated with breast conservation therapy. Of the SBBC patients, 13 of 16 patients received breast-conserving therapy for both breasts, while 3 received a mastectomy for the second synchronous primary. Median follow-up was 50 months for SBBC patients, 45 months for MBBC patients, and 52 months for UBC patients. Local control and survival were analyzed in patients with SBBC, MBBC, and UBC. The interval to development of local recurrence and survival were calculated from the time of development of the second breast lesion in patients with MBBC. No differences were found for survival and failure-free survival in patients with SBBC, MBBC, or UBC. Five-year overall survival by lifetable analysis was 76% for SBBC, 78% for MBBC, and 87% for UBC patients (p = 0.32 by log-rank analysis). The 5-year failure-free survival was 79% for SBBC, 73% for MBBC, and 85% for UBC patients (p = 0.28 by log-rank analysis). No significant differences were seen for median age, tumor size, pathologic node status, tamoxifen use, chemotherapy use, or median total radiation dose for SBBC, MBBC, or UBC patients. A significant difference was found in the incidence of family history of breast cancer in patients with unilateral versus bilateral breast cancer (p = 0.028 by chi-square analysis). However, there was no difference in outcome of patients by family history of breast cancer. The local control was identical in both BBC and UBC patients, with a local failure rate of 3%. Therefore, breast conservation therapy in local-regional, early stage breast cancer is a rational and efficacious treatment modality for patients with SBBC, MBBC, and UBC.     

Geographic Differences in Treatment of Early Stage Breast Cancer

The objective of this study was to describe recent time and geographic variations in breast cancer treatment while controlling for patient age, race, and ethnic group. Treatment data for women diagnosed with localized breast cancer from nine defined geographic areas of the United States from 1983 through 1992 were analyzed. Of 80,887 subjects, 33.9% were treated with lumpectomy from 1983 to 1992. The proportion of women treated with lumpectomy varied greatly according to geographic area, ranging from overall percentages of 19.0% in Iowa to 41.4% in Connecticut, but increased in all sites during the time period under study. Women less than 50 years and more than age 80 years and older were most likely to have lumpectomy, while Asian/Pacific islander women were significantly less likely compared to Caucasian women. Rates for African American and Hispanic women were not significantly different than those for Caucasian women. Although consensus conferences and randomized clinical trials have indicated lumpectomy is appropriate therapy for the majority of women diagnosed with early stage breast cancer, large geographic differences in rates have persisted over time. These differences were not explained by underlying differences in age or race distributions in the geographic areas included in this study. ▪     

Pilot Study of Low-Dose,Divided Maximum Tolerated Dose of CPT-11 in 21 Consecutive Patients with Metastatic Colorectal or Gastric Cancer

Purpose We devised a new treatment regimen, delivering a frequent low dose of CPT-11, calculated by dividing the maximum tolerated dose (MTD) to reduce its toxicity without impairing its efficacy.Methods CPI-11, 25mg/m², determined by dividing the MTD dose per month by 12, was given on days 1, 2, and 3 of every week, to 21 consecutive patients; 12 with metastatic colon cancer and 9 with metastatic gastric cancers.Results The total delivered dose of CPI-11 per patient was more than 1000mg in 17 (80.1%) of the 21 patients. Grade 3 marrow depression developed in 3 (14.3%) patients, and although nausea, vomiting, alopecia, and diarrhea developed in some patients, these side effects were all categorized as grade 2 or milder. The antitumor effect was evaluated in 18 patients with measurable lesions, who had received CPI-11 according to our regimen for at least 3 weeks. Of these 18 patients, 10, 7, and 1, respectively, had a found to have partial response, no change, or progression of disease, demonstrating a 55.6% efficacy rate [colon 6/10 (60.0%) and stomach 4/8 (50.0%)]. Moreover, time to progression (TTP) was greater than 90 days in 12 (75.0%) of these 18 patients.Conclusion These results show that our low-dose, divided MTD of CPI-11 regimen is a promising method of reducing toxicity and strengthening the antitumor effect, justifying further large-scale comparative clinical studies to verify this potential.     

The Department of Defense Experience in Perioperative Testing for Metastatic Disease in Patients with Breast Cancer

Abstract: Although multiple tests are often performed prior to surgery for the primary treatment of breast cancer, the role of perioperative testing has yet to be clearly defined. The purpose of this study was to examine the use of perioperative testing in the Department of Defense (DOD) health care system. Records from all patients who received an operation for breast cancer between April 1, 1990 and March 1, 1992 in the DOD health care system were reviewed. The results of bone scans (BS), abdominal CT scans, brain scans (CT, MRI), chest radiographs (CXR), blood tests, and specified parameters from the history and physical examination were analyzed. Chi-square statistics were performed. 2,364 women underwent surgery for breast cancer during this period. The percentage of patients that received each test (A) and the percentage of the tests that were suggestive of metastatic disease (B) are as follows ([A%], [B%]): CXR (94%, 1.3%); BS (23%, 8%); abdominal CT (4%, 9%); and brain scans (1%, 11%). There were more abnormal BS in patients with an elevated alkaline phosphates than in those with a test that was normal or never performed (20% vs. 4.8%, p < 0.001). Elevated liver function tests or central nervous system signs or symptoms were not associated with abnormal studies. In the past, patients with breast cancer underwent an extensive array of blood tests, CXR, and scans of bones, liver, and brain in the attempt to detect occult metastatic disease prior to surgery. In a large and diverse system such as the DOD, however, a perioperative metastatic work-up, which includes a BS, brain scan, and abdominal CT scan is not routinely performed, suggesting that clinicians selectively perform specific tests during this period. Despite this tendency, when tests are performed on breast cancer patients in the perioperative period, they are infrequently suggestive of metastatic disease.     

Differentiation of the Mammary Epithelial Cell during Involution: Implications for Breast Cancer

That milk secretion is not the final differentiated state of the mammary alveolar cells is a relatively new concept. Recent work has suggested that secreting, mammary epithelial cells (MECs) have another function to perform before they undergo cell death in the involuting mammary gland. That is, they help in the final clearance and breakdown of their neighboring cells (and likely residual milk as well.) They become, for a short time, amateur phagocytes, or efferocytes, and then are believed to die and be cleared themselves. Although relatively little study has been made of this change in the functional state of the MEC, nevertheless we may speculate from the involution literature, and extend findings from other systems of apoptotic cell clearance, on some of the mechanisms involved. And with the finding that involution may represent a unique susceptibility window for the progression of metastatic breast cancer, we may suggest areas for future research along these lines as well. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Detection and Significance of Occult Axillary Metastatic Disease in Breast Cancer Patients

▪ Abstract: After clinical staging, the single most important prognostic factor for patients with newly diagnosed primary breast cancer is the presence or absence of detectable metastases to axillary lymph nodes when examined by conventional light microscopy. More sensitive methods of determination of lymph node status, such as evaluation of serial sections, immunohistochemical staining, and use of molecular biological assays increase the rate of detection of micrometastases. Although the feasibility of enhanced detection of occult axillary metastatic disease is well established, the prognostic significance of such detection is only recently starting to emerge. Furthermore, the enormous recent interest in the application of sentinel lymph node biopsy as an alternative to the evaluation of the entire axilla in patients with breast cancer makes the first-time detailed evaluation for micrometastases practically feasible. In this review the different methods of detecting micrometastatic disease in the axilla and the significance of such findings are discussed. ▪     

不同术式对T_1乳腺癌病人的疗效评估

目的：探讨不同术式对Ｔ１乳腺癌的疗效。方法：观察Ｈａｌｓｔｅｄ术、改良根治术和乳房象限切除加腋淋巴结清扫术对２７４例Ｔ１乳腺癌病人预后的影响;并分析全部病人的腋淋巴结转移情况。结果：Ｔ１乳腺癌病人１０年生存率为８４．７％;标准根治术与改良根治术后病人的１０年生存率分别为８０．５石％和８４．１％（Ｐ＞０．０５）;乳房象限切除加腋淋巴结清除术与根治术相比,Ｔ１Ｎ０Ｍ０病人的１０年生存率分别为１００％和９０．４％（Ｐ＞０．０５）;全组腋淋巴结转移率为２７．７％;９７．４％的转移淋巴结位于低位组。结论：３种术式治疗Ｔ１乳腺癌病人的效果相同,从美观及心理因素上考虑,提倡行保守性手术;２／３以上Ｔ１病人无腋淋巴结转移,一律行腋淋巴结清除对预后意义不大,前哨淋巴结活检可以解决这一问题;腋淋巴结转移绝大多数在低位组,在不能进行前哨淋巴结活检的情况下,可仅清除低、中位淋巴结。     

Delay in Presentation,Diagnosis, and Treatment for Breast Cancer Patients in Jordan

Breast cancer is the most common cancer, and one of the leading causes of death for females in Jordan and many countries in the world. Studies have shown that delay in symptoms presentation, diagnosis or treatment would result in poor prognosis. There has been no published study from Jordan on delays in patient presentation, delays in diagnosis, or delays in treatment. Therefore, we conducted this study to assess these important quality indicators aiming to improve prognosis for breast cancer patients in Jordan. This project was a cross‐sectional study on female breast cancer patients in Jordan. The total number of participants was 327. The proportion of patients with presentation delay, diagnosis delay, and treatment delay was 32.2%, 49.1%, or 32.4%, respectively. The main reported reasons for delay in presentation were ignorance of the nature of the problem (65.6%), limited/lack of knowledge that symptoms were suggestive of cancer diagnosis (16.7%), and misdiagnosis (16.7%). Predictors of delay and mean time for presentation, diagnosis, and treatment were identified. Our results reveal that breast cancer patients in Jordan are experiencing delays in presentation, diagnosis, and treatment. This could justify the advanced stages at diagnosis and poor outcomes for breast cancer patients in Jordan. We recommend revising the current early detection and down‐staging programs in Jordan.