Nipple-sparing mastectomy in breast cancer: a viable option?

BACKGROUND: In women with breast cancer for whom breast-conserving therapy (BCT) is not the best option, a nipple and areola complex-(NAC) sparing mastectomy with immediate reconstruction has been proposed as a good and safe alternative to conventional, more radical mastectomy. Surgeons hesitate to perform this operation for fear of recurrence of tumour in the NAC due to undetected nipple involvement (NI) of the tumour. In order to determine whether a NAC-sparing mastectomy is a viable option, the frequency and predictive factors of NI by the tumour were studied in the literature. METHODS: A literature survey was performed by searching the Medline database. Other references were derived from the material perused. RESULTS AND CONCLUSIONS: NI is found in up to 58% of mastectomy specimens and correlates with tumour size, tumour-areola or tumour-nipple distance, positive lymph nodes and clinical suspicion. Best candidates for NAC-sparing mastectomy are patients with a small tumour (T1) at a large distance (>4-5 cm) from the nipple. However, in these patients BCT has excellent results with low complications and recurrence rates. Considering the incidence of NI in larger tumours (T2 average 33%, T3 average >50%) a NAC-sparing mastectomy may carry an unacceptable high risk for local relapse and should therefore not be advocated.     

Adjuvant bisphosphonate treatment for breast cancer: Why did something so elegant become so complicated?

Bisphosphonate therapy has revolutionized the care of patients with metastatic bone disease. With its demonstrated activity and anti-tumour effects in preclinical studies it was natural to transition these agents to testing in the adjuvant setting. Surprisingly, the results of adjuvant breast cancer trials have shown either modest or no benefit or even harm. We sought to explore whether there were specific patient cohorts or treatment strategies that were most likely to benefit from adjuvant bisphosphonate therapy. We compared trial designs, patient characteristics and outcomes from the six published and two presented randomized adjuvant bisphosphonate trials. Differences in trial design and patient populations make direct comparisons complicated. The most efficacious use of adjuvant bisphosphonates appears to be in patients with either biopsy evidence of osseous micrometastases, were post-menopausal or had estrogen receptor-positive tumours. Despite tremendous optimism regarding adjuvant bisphosphonate therapy, results from large trials are conflicting. Further investigation into factors influencing response to bisphosphonate treatment or selection of appropriate sub-groups of patients with desirable response characteristics is warranted.     

Why do hospital mastectomy rates vary? Differences in the decision-making experiences of women with breast cancer

Background:

Hospital mastectomy rates vary. This study explores the relationship between mastectomy rates and breast cancer patients'' consultation and decision-making experiences with specialist clinicians.

Methods:

Qualitative semi-structured interviews were conducted with 65 patients from three purposively selected breast units from a single UK region. Patients provided with a choice of breast cancer surgery (breast conservation therapy (BCT) or mastectomy) were purposively recruited from high, medium and low case-mix-adjusted mastectomy rate units.

Results:

Low mastectomy rate unit patients'' consultation and decision-making experiences were markedly different to those of the medium and high mastectomy rate breast units. Treatment variation was associated with patients'' perception of the most reassuring and least disruptive treatment; the content and style of information provision (equipoise or directed); level of patient participation in decision making; the time and process of decision making and patient autonomy in decision making. The provision of more comprehensive less directive information and greater autonomy, time and support of independent decision making were associated with a lower uptake of BCT.

Conclusion:

Variation in hospital mastectomy rates was associated with differences in the consultation and decision-making experiences of breast cancer patients. Higher mastectomy rates were associated with the facilitation of more informed autonomous patient decision making.     

Short course radiotherapy and delayed surgery for locally advanced rectal cancer in frail patients: is it a valid option?

ObjectiveThe endpoint of the present study was to evaluate the outcomes of short-course radiotherapy (SCRT) and SCRT with delayed surgery (SCRT-DS) on a selected subgroup of frail patients with locally advanced middle/low rectal adenocarcinoma.MethodsFrom January 2008 to December 2018, a total of 128 frail patients with locally advanced middle-low rectal adenocarcinoma underwent SCRT and subsequent restaging for eventual delayed surgery. Rates of complete pathological response, down-staging, disease free survival (DFS) and overall survival (OS) were analyzed.Results128 patients completed 5 × 5 Gy pelvic radiotherapy. 69 of these were unfit for surgery; 59 underwent surgery 8 weeks (average time: 61 days) after radiotherapy. Downstaging of T occurred in 64% and down-staging of N in 50%. The median overall survival (OS) of SCRT alone was 19.5 months. The 1-year, 2-year, 3-year and 5-year OS was 48%, 22%, 14% and 0% respectively. In the surgical group, the median disease-free survival (DFS) and median OS were, respectively, 67 months (95% CI 49.8–83.1 months) and 72.1 months (95% CI 57.5–86.7 months). The 1, 2, 3, 5-year OS was 88%, 75%, 51%, 46%, respectively. Post-operative morbidity was 22%, mortality was 3.4%.ConclusionsFrail patients with advanced rectal cancer are often “unfit” for long-term neoadjuvant chemoradiation. A SCRT may be considered a valid option for this group of patients. Once radiotherapy is completed, patients can be re-evaluated for surgery. If feasible, SCRT and delayed surgery is the best option for frail patients.     

Neoadjuvant endocrine therapy for breast cancer: an overlooked option?

For many oncologists, neoadjuvant treatment for breast cancer is synonymous with preoperative cytotoxic chemotherapy, regardless of tumor characteristics. Preoperative therapy with an endocrine agent is generally considered suitable only for the frail elderly or the medically unfit. However, favorable information regarding third-generation aromatase inhibitors in the treatment of all stages of breast cancer prompts a reconsideration of this bias. In light of the fact that neoadjuvant therapy with aromatase inhibitors is restricted to postmenopausal women with strongly estrogen-receptor-positive tumors, the assumption that neoadjuvant combination chemotherapy is more efficacious than a third-generation aromatase inhibitor can be reasonably questioned. It is particularly remarkable that the outcome of a comparison of adjuvant tamoxifen vs anastrozole (Arimidex)--the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial--in more than 6,000 patients was predicted by a neoadjuvant trial that showed an efficacy advantage for a third-generation aromatase inhibitor (letrozole [Femara]) compared to tamoxifen in a sample of 337 patients after only 4 months of treatment. The potential of the neoadjuvant setting in efforts to identify new biologic agents that could build on the effectiveness of adjuvant aromatase inhibitors is therefore beginning to be appreciated. Finally, neoadjuvant therapy with an aromatase inhibitor could be considered a sensitivity test of endocrine therapy that might be incorporated into strategies to individualize treatment according to response. For this possibility to be realized, however, a better understanding of the relationship between surrogates from the neoadjuvant setting and the long-term outcome of adjuvant aromatase inhibitor therapy will have to be established through practice-setting clinical trials.     

Gemcitabine plus docetaxel: a new treatment option for anthracycline pretreated metastatic breast cancer patients?

Antimetabolite-taxane combinations have been shown to be effective chemotherapy in patients with metastatic breast cancer (MBC). A multicentre phase III trial comparing gemcitabine-docetaxel with capecitabine-docetaxel in women with anthracycline pretreated MBC was carried out in several European countries. Its results were presented recently [1]. One-hundred and fifty-three patients were randomly assigned to receive docetaxel (75 mg/m2, day 1) plus gemcitabine (1000 mg/m2, days 1, 8) and 152 received docteaxel plus capecitabine (1250 mg/m2, bid days 1-14) every 3 weeks until disease progression. No difference in efficacy of the two treatment regimens was observed in terms of progression-free survival (35 weeks in both treatment arms), overall response rate (32% vs. 32%), time to treatment failure (19 vs. 18 weeks, respectively), or response duration (36 vs. 42 weeks). Drug-related toxicity, particularly hand-foot syndrome, mucositis and diarrhoea, was more frequent with capecitabine-docetaxel and there was a higher incidence of drug-related treatment withdrawals with this combination. Gemcitabine-docetaxel appeared to have a more favourable risk-benefit profile than capecitabine-docetaxel, and is an important new treatment option for women with anthracycline-pretreated MBC.     

Quality of life of breast cancer patients and types of surgery for breast cancer — Current status and unresolved issues —

Since standard radical mastectomy was established by Halsted for breast cancer, surgical procedures for breast cancer have been changed according to the results of randomized controlled trials. Breast-conserving treatment is now regarded as a standard local treatment for early breast cancer. More recently, sentinel node biopsy is becoming popular as an alternative procedure to axillary node dissection for nodal staging. These new procedures have been believed to be better in terms of patients' quality of life in comparison with previous surgical procedures without impairing prognosis.Many studies regarding the quality of life (QOL) of patients after such procedures have been reported. Here we review those data, especially of studies comparing quality of life of patients after mastectomy and breast-conserving treatment, and of those after axillary node dissection and sentinel node biopsy. Viewpoints and issues on surgical treatment-related QOL are discussed.     

The effect of delayed treatment in breast cancer patients: How much is too late? An experience of a single-center study effect of surgery delay in survival

Background and objectivesProper treatment is critical for control and curative intent in breast cancer. Delays in receiving treatment can influence patients' prognoses.MethodsRetrospective, observational, single-center study based on data from medical records of 747 patients with non-metastatic invasive ductal breast carcinoma (I-III) in the initial analysis, comprising 554 patients undergoing adjuvant and 193 neoadjuvant treatment. Kaplan-Meier, Cox regression and time-dependent Cox regression were performed to obtain the predictive value of time to surgery and time to first treatment. Immortal time bias was managed and only 721 patients were included in the multivariable analysis.ResultsDuring a median observation of 64.4 months, there were 140 death events and 177 disease progression events. Time to surgery (TTS) and time from completion of neoadjuvant chemotherapy to surgery (TNS) showed a significant impact on overall survival, associated with a 6% increased chance of death [HR: 1.06 (1.03–1.09), p < 0.001] and 4% [HR: 1.04 (1.00–1.09), p = 0.048] with a one-month increment, respectively. By multivariable analysis, continuous TTS had a different weight as a prognostic factor in stage IIIA/IIIB [adjusted HR: 1.249 (1.072–1.454), p = 0.004] compared to stage I/II [adjusted HR: 1.093 (1.048–1.141), p < 0.0005]. Likewise, TNS was significant after adjusting for other factors [adjusted HR: 1.092 (1.038–1.148), p = 0.001].ConclusionDelay in receiving surgery with curative intent impairs the survival of patients with breast cancer.     

Multiple foci of invasive breast cancer: can breast MRI influence surgical management?

The use of MRI to assess the extent of breast disease is gaining increasing popularity with the subsequent detection of multiple invasive foci within the breast that had not been identified on previous standard mammography and ultrasonography. What impact this has on subsequent surgical management and ultimately disease-free survival remains a controversial topic. Should histologically confirmed multiple foci of invasive disease within a breast steer the surgical management towards mastectomy, or is there a role in select patients for breast conserving surgery, even if two or more incisions are required? This review considers the evidence for how MRI affects the mastectomy rate and compares this to surgical outcomes for breast conserving surgery in the presence of multiple invasive foci.     

President’s address: Minimally invasive treatment for patients with early breast cancer

Summary  We think that minimally invasive treatments, such as lumpectomy, SLNB or minimal invasive dissection can reduce the duration of stay in the hospital to a same-day surgery. In our questionnaire to patients, 63% responded that hospital stay of 2 days was too short of 2 days, because patients in Japan still appreciate a longer stay in hospital. We encourage patients to do everything to detect-come in with breast cancer on the early stage, as it is possible to provide treatment much more successfully. If breast cancer can be detected at on early stage, it is possible to treat patients more conservatively. Breast cancer screening by mammography should be included as an important part of the whole health care system.     

Neoadjuvant chemotherapy for operable breast cancer: is this the future?

The idea of using preoperative or neoadjuvant chemotherapy in patients with operable breast cancer originated from experimental and clinical observations as well as theoretical hypotheses on tumor cell growth and dissemination. Initially, nonrandomized studies demonstrated considerable rates of clinical tumor response, low rates of pathologic complete response (pCR), and increased rates of breast-conserving procedures. However, nonrandomized studies could not address the relative efficacy of neoadjuvant versus adjuvant chemotherapy on disease-free and overall survival. Similarly, earlier randomized trials were not designed as straightforward comparisons of neoadjuvant versus adjuvant chemotherapy and therefore could not adequately address the relative efficacy of neoadjuvant versus adjuvant chemotherapy on outcome. These answers were eventually provided by larger randomized trials that directly compared neoadjuvant with adjuvant chemotherapy, which are reviewed in more detail in this article. Potential advantages and disadvantages of the neoadjuvant approach and surgical considerations in the breast and axilla after neoadjuvant chemotherapy are also discussed. Finally, several recently reported trials of neoadjuvant therapy incorporating newer agents such as taxanes in sequence with anthracycline-containing regimens have shown further increases in pCR rates. Although outcome data are not available yet from these studies, it is hoped that the observed increase in pCR rates will be associated with improved outcome. If the previously observed significant correlation between the achievement of pCR and improved outcome continues to be demonstrated with these newer regimens, it will substantially strengthen the rationale for using neoadjuvant rather that adjuvant chemotherapy in the clinical setting as well as in future research studies.     

Alternative therapies for curing cancer: what do patients want? What do patients need?

Despite her scientific training and experience in medical practice, after being diagnosed with an indolent non-Hodgkin's lymphoma, the author was subjected to intense pressure about alternative therapies from well-meaning friends and relatives. While insulated at first from these forces, disease recurrences and progression increased her vulnerability to the lure of seemingly gentler approaches. A data-driven study of alternative therapeutic methods, however, convinced the author that investigational strategies offered her a better chance of cure or improvement than unproven alternative methods. She offers guidelines for physicians about what patients want, and emphasizes the importance of hope, caring, and information.