Surgery For Operable Breast Cancer Research Articles

Abstract ES8-4: Axillary management in upfront surgery - staging, local control or both?

Abstract Axillary management in women undergoing upfront surgery for operable breast cancer has changed dramatically over the last several decades. Axillary lymph node dissection (ALND), a procedure that was historically used in both clinically node negative and node positive patients to stage the axilla and optimize locoregional control, is associated with the potential for significant long-term morbidity in the form of upper extremity lymphedema, paresthesia, and shoulder dysfunction. Efforts to minimize the morbidity associated with ALND, as well as the recognition that only a minority of patients with clinically node negative disease are found to have nodal metastases at the time of axillary surgery, prompted the development and validation of sentinel lymph node biopsy (SLNB). In women who are clinically node negative, SLNB has been shown to accurately stage the axilla without compromising oncologic outcomes, identifying nodal disease in up to 30% of cases. The application of clinical trial data from Z0011 and AMAROS in T1-T2 breast cancer with 1-2 positive lymph nodes undergoing breast conservation allow for omission of completion ALND with no impact on locoregional control or survival. The ongoing POSNOC trial (NCT02401685) will further determine whether women with T1-T2 disease undergoing breast conservation or mastectomy require directed axillary treatment in the form of ALND or axillary radiation to minimize the risk of axillary failure. An altogether omission of axillary staging in clinically node negative breast cancer remains an area of evolving interest, with CALGB 9343 trial data supporting this approach in older women with stage I estrogen-receptor positive (ER+) HER2- breast cancer. Trials examining the omission of SLNB in other select patient populations with negative axillary imaging are the subject of ongoing investigation. At present, prognostic information derived from SLNB for clinically node negative women undergoing upfront surgery for early-stage triple negative and HER2+ breast cancer, premenopausal ER+HER2- breast cancer, and BRCA1/2-associated breast cancer remain important for adjuvant systemic therapy decision-making. Citation Format: S Wong. Axillary management in upfront surgery - staging, local control or both? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES8-4.

Defer surgery in operable breast cancer: how long is too long?

PurposeThe aim of this meta-analysis was to evaluate outcomes of surgery compared to primary endocrine therapy (PET) in patients with non-advanced, operable invasive breast cancer, and to determine if PET as initial therapy may safely postpone surgery.MethodsThe MEDLINE, EMBASE, PubMed, and Cochrane Library were searched from database inception to July 2020 to identify eligible studies. Inclusion criteria were experimental or observational studies with at least one arm treated with PET and a second arm treated with surgery with or without PET. Local recurrence or progression of disease was defined as either failure of non-operative management (tumor failing to decrease in size and/or continuous local or distant tumor growth) or relapse of breast tumor after tumor downsizing following PET. Effect estimates were expressed in hazard ratio and 95% confidence intervals (HR (95% CI)).ResultsThe analysis included six studies with 1499 unique patients. The median time to local progression of disease was 2.3 years. Patients treated with PET alone without surgery had a higher risk of local recurrence and or progression [HR (95% CI): 1.76 (1.33, 2.31); I2 = 84%; p < 0.001]. Patients treated with PET had more favorable outcomes in terms of overall survival [HR (95% CI): 1.24 (1.06, 1.46); I2 = 70%; p = 0.008] and less favorable outcomes in breast cancer-specific survival [HR (95% CI): 1.13 (0.98, 1.31); I2 = 41%; p = 0.10]. The risk of publication bias was assessed to be high in reporting local recurrence rates and low in reporting distant recurrence rates.ConclusionPET alone is inferior to surgery in the treatment of operable invasive breast cancer.However, it may be acceptable to postpone curative breast cancer surgery without risk of progression for 1.1 years or longer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12282-021-01302-4.

Patients electing to have PET rather than surgery for operable breast cancer are a high risk of treatment failure.

Primary endocrine therapy (PET) is a treatment option for elderly patients with ER-positive breast cancer enabling frail patients to avoid surgery. As a long-term treatment option, it has been shown to be inferior to surgery in controlling local disease. Decision-making in these patients is crucial in avoiding treatment failure. We examined the influence of decision-making on outcomes of PET failure as a secondary analysis as part of a large observational study. Consecutive patients treated with PET between 2005 and 2015 for operable breast cancers were included in a retrospective observational study in 3 breast centres in the North-East. Treatment decision processes were examined by case note review and outcomes of treatment success or failure recorded. 488 patients were included with mean follow-up of 31months. Overall 63 (12%) experienced treatment failure. 227 (46.6%) were given a choice between surgery and PET at diagnosis. Logistic regression identified older age [OR 0.94 (0.91-0.96) p < 0.001] and reduced mobility [OR 0.6 (0.37-0.97) p 0.036] to be less likely offered surgery. Those offered surgery were more likely to experience treatment failure with PET [SHR 1.78 (1.05-3.02) p 0.033]. Despite a low failure rate in our series (literature failure rates vary between 12 and 85%), these results suggest that those actively offered a choice between surgery and PET are at greater risk of failure when choosing PET.

Abstract 495: The impact of preoperative hydroxyprogesterone on serial levels of circulating tumor cells [CTCs] in patients undergoing surgery for operable breast cancer

Abstract Introduction: Assessment of Circulating Tumour Cells [CTCs] from the peripheral blood of patients diagnosed with cancer is emerging as a valuable biomarker for prognostication and tailoring therapy. A previous study demonstrated that a single depot injection of hydroxyprogesterone prior to surgery improved the DFS of patients with large tumours or positive nodes, forming the basis for this investigation, designed to assess effects of this drug on serial levels of CTCs on patients with operable breast cancer. Methods: Seventy patients were enrolled, randomized, and as previously described a single depot injection of hydroxyprogesterone was administered prior to surgery in patients in the experimental arm. Peripheral blood samples were obtained at three time points during surgery; prior to induction of anaesthesia, intra operative and at completion. Peripheral Blood Mononuclear Cell [PBMC] fractions separated on Ficoll hypaque were enriched for tumour cells with double positive immunomagnetic selection for EpCAM [Epithelial Cell Adhesion Molecule]. Half the enriched fraction was routed for multistep sequential labelling of cell-surface markers; EpCAM and CD45, cytoplasmic Cytokeratin and staining with DAPI for the nucleus, facilitating acquisition with multi parametric flow cytometry and imaging using confocal microscopy. With pre-amplification of other half of the enriched fraction, a quantitative expression analysis for a panel of epithelial genes was performed. Results:With multi parametric flow analysis, events that were CD45-/ EpCAM+/ CK+ with DAPI positivity were defined as CTCs, reported as events/ml blood and in all samples were in the range of 0 to 155 /ml of blood with no significant difference observed between the two arms. Detailed analysis with pooled data of all time points, in premenopausal patients, using the Mann Whitney test, showed that the mean number of CTCs is significantly lower[p = 0.005] in the experimental arm[n = 30] as compared to the control arm[n = 36] .Analysis within the hydroxyprogesterone group using the Wilcoxon signed rank test showed that the mean number of CTCs is lower in the post-surgery time point when compared to the pre surgery time point, in patients with positive nodes[n = 16][p = 0.044], large tumours [n = 18] [NS; p = 0.085] and post-menopausal node positive group [n = 7] [NS; p = 0.063] The expression analysis for the selected markers and confocal images validated the identity of tumour cells. Conclusions: Patient follow-up will ascertain the benefits of reduced numbers observed and establish CTCs as a surrogate marker for prognostication. Citation Format: Ujjwala M. Warawdekar, Vani Parmar, Akshita Singh, Swapnil Aher, Abhay Kulkarni, Meenal Chaudhari, Sudeep Gupta, Rajendra A. Badwe. The impact of preoperative hydroxyprogesterone on serial levels of circulating tumor cells [CTCs] in patients undergoing surgery for operable breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 495.

A population based study of variations in operation rates for breast cancer, of comorbidity and prognosis at diagnosis: Failure to operate for early breast cancer in older women

BackgroundOlder women are less likely to have surgery for operable breast cancer. This population-based study examines operation rates by age and identifies groups which present with early or late disease. Methods37 000 cancer registrations for 2007 were combined with Hospital Episode Statistics comorbidity data for England. Operation rates were examined by age, ethnicity, deprivation, comorbidity, screen-detection, tumour size, grade and nodal status. Early and late presentation were correlated with Nottingham Prognostic Index (NPI) groups and tumour size. ResultsThe proportion of women not having surgery increased from 7–10% at ages 35–69 to 82% from age 90. From age 70, the proportion not having surgery rose by an average of 3.1% per year of age. Women with a Charlson Comorbidity Index score of ≥1 (which increased with age), with tumours >50 mm or who were node positive, were less likely to have surgery. Although women aged 70–79 were more likely to have larger tumours, their tumours were also more likely to have an excellent or good NPI (p < 0.001). Good prognosis tumours were more likely to be screen-detected, and less likely in women aged 0–39, the deprived and certain ethnic groups (p < 0.02). ConclusionsFrom age 70 there is an increasing failure to operate for breast cancer. Younger women and certain ethnic groups presented with more advanced tumours. Older women had larger tumours which were otherwise of good prognosis, and this would not account for the failure to operate which may in part be related to comorbidity in this age group.

353P - The Prognostic Meaning of Protein Tyrosine Phosphatase Non-Receptor Type 12 (PTPN 12) Expression Loss in Breast Cancer Patients

ABSTRACT Background Recent preclinical studies showed that protein tyrosine phosphatase non-receptor type 12 (PTPN 12) appears to be an important tumor suppressor in breast cancer. However, the clinical and prognostic significance of PTPN 12 expression in breast cancer patients has not been elucidated yet. Methods PTPN 12 expression status was assessed for 183 patients who underwent curative surgery for operable breast cancer between May 2000 and August 2003, using immunohistochemical (IHC) assay of tissue microarray. Clinicopathologic characteristics, and expression status of ER, PR, EGFR, HER-2 were compared according to PTPN 12 expression status. The prognostic significance of PTPN 12 expression on disease-free survival (DFS) and overall survival (OS) was analyzed and the prognosis was also assessed in subgroups defined on the basis of major prognostic factors and ER, PR, HER-2, EGFR expression status. Results Loss of PTPN 12 expression was observed in 35.5% of the patients in this study. No significant differences were found in the clinicopathological characteristics and ER, PR, HER-2, EGFR expression status between PTPN 12 loss versus PTPN 12 intact patients. At a median follow-up of 9.9 years (range, 0.7-11.1), patients with PTPN 12 loss showed worse 10-year DFS than those with intact PTPN 12 expression (74.8% vs. 83.1%), but without statistical significance (p = 0.220). Ten-year overall survival of patients was not different according to PTPN 12 expression status. In the subgroup analysis performed in HER2 (-) and EGFR (-) patients (n = 128), the DFS was shorter in patients with PTPN 12 loss in univariate analysis (p = 0.057), and the difference was independently significant in multivariate analysis (hazard ratio, 2.97; 95% confidence interval, 1.05-8.37; p = 0.040). In the subgroup of patients who received hormone therapy alone as adjuvant treatment (n = 28), all recurrences were occurred in patients with PTPN 12 loss (5 recurrence in 16 patients) whereas there was no recurrence in patients with intact PTPN 12 expression. Conclusion PTPN 12 expression loss was associated to poor disease free survival in HER2 negative and EGFR negative breast cancer patients in this study. Our finding suggests that PTPN 12 may have a prognostic meaning predicting recurrence in HER2 negative and EGFR negative breast cancer patients, and future validation is warranted. Disclosure All authors have declared no conflicts of interest.

Older women with operable breast cancer are less likely to have surgery

Older women are less likely to receive standard management for breast cancer than younger postmenopausal women. Whether differences in general health explain variations in the rates of surgery is not known. In this prospective cohort study, 76 women aged 65 years or more attending breast units in Greater Manchester completed a survey measuring functional status (Elderly Population Health Status Survey's Activity of Daily Living), generic health status (Short Form 12) and health-related quality of life (European Organization for Research on Treatment of Cancer Quality of Life Questionnaire C30). Case-note review assessed co-morbidity (Charlson Index) and management. Primary surgery for operable breast cancer was investigated using logistic regression. A Charlson Index of 1 or more did not predict the use of surgery (P = 0.363). However, for each point increase on the 1-4 scale indicating worsening functional status, the odds of having surgery decreased by 16 times (odds ratio 0.063). The odds of a woman of 80 years or more having surgery decreased by a factor of 44 (odds ratio 0.023) compared with women aged 65-79 years, accounting for co-morbidity, functional status, pretreatment stage, social deprivation and type of hospital. Older women were less likely to have surgery for operable breast cancer than younger women, even after accounting for differences in general health and co-morbidity.

The National Health Service Breast Screening Programme in the Trent region—are we meeting the targets?

Aims In the UK National Breast Screening Programme, women aged 50–64 years are invited for breast screening mammography. This study aimed to determine whether current quality assurance guidelines for the Breast Screening Programme were being achieved. Method A prospective analysis of key outcome measures was performed in the 11 breast screening units in the Trent region, between 1 January 1995 and 31 December 1995. Results All 11 units exceeded the 70% target for screening attendance. Ten units matched the invasive cancer detection target for the prevalent screen, but this fell to three for the incident screen. Seven units achieved the 50% target for small invasive cancers, but for special type and well-differentiated cancers only three units matched the target of 30% and there was wide variation between units. Pre-operative diagnosis rates were short of targets in most units. Only one unit achieved outcome measures for clear histological margins in patients completing operations for breast-conserving surgery. No unit provided histological node status on all its patients undergoing surgery for operable breast cancer, or met the target for benign biopsy weights. Conclusion Although results as a whole are good, changes can be made to improve performance and reduce the variation between units. Particular attention should focus on those areas which can be influenced directly by surgeons. In the UK National Breast Screening Programme, women aged 50–64 years are invited for breast screening mammography. This study aimed to determine whether current quality assurance guidelines for the Breast Screening Programme were being achieved. A prospective analysis of key outcome measures was performed in the 11 breast screening units in the Trent region, between 1 January 1995 and 31 December 1995. All 11 units exceeded the 70% target for screening attendance. Ten units matched the invasive cancer detection target for the prevalent screen, but this fell to three for the incident screen. Seven units achieved the 50% target for small invasive cancers, but for special type and well-differentiated cancers only three units matched the target of 30% and there was wide variation between units. Pre-operative diagnosis rates were short of targets in most units. Only one unit achieved outcome measures for clear histological margins in patients completing operations for breast-conserving surgery. No unit provided histological node status on all its patients undergoing surgery for operable breast cancer, or met the target for benign biopsy weights. Although results as a whole are good, changes can be made to improve performance and reduce the variation between units. Particular attention should focus on those areas which can be influenced directly by surgeons.

Postmastectomy radiotherapy in the management of operable breast cancer.

There is a long and detailed history of radiation therapy as an adjuvant to surgery in operable breast cancer. The results of a large number of randomized clinical trials will be reviewed. They can be summarized by saying that although the trials show a reduction in local-regional failure with the use of postoperative radiotherapy, a survival advantage has not been clearly identified. Many of the older trials used techniques and radiation doses inadequate by current standards, which may have affected the results. Recent trials that used therapeutic doses of radiation, however, did demonstrate a survival advantage among patients who received postoperative radiotherapy. These trials generally have included chemotherapy and required careful integration of radiotherapy and systemic therapy. Although all trials have not demonstrated a survival benefit by the addition of radiotherapy, the ability to maintain local-regional control after mastectomy is an important goal. Administration of prophylactic chest wall and nodal radiotherapy to patients at high risk for local-regional recurrence significantly reduces the chance of a local treatment failure. Because a chest wall recurrence is a distressing event that dramatically affects quality of life, improved local-regional control with postoperative radiotherapy is a highly significant end point.

Reconstructive surgery in operable breast cancer. Critical evaluation.

In a large number of patients suffering from breast carcinoma the surgeon is still forced, for strictly technical reasons and/or by the patient's choice, to perform a radical operation that psychologically and practically compromises the quality of life of the patient, in varying degrees from patient to patient. The authors have analyzed the main characteristics of BR from the esthetic-functional, psychological, and oncological points of view, in the light of a careful examination of the literature and of the data relating to a sample group of 500 BR treated according to a protocol in which BR has been included, with times and modalities depending on the histological type of tumor and the level of local evolution of the disease. The variety of BR techniques available is such as to permit this option in a great variety of cases. Whenever possible, immediate BR, with placement of a breast prosthesis at the same time or after positioning a tissue expander, is to be preferred. If additional skin or muscle is needed, BR is to be performed at a later time by means of more complex techniques (latissimus dorsi myocutaneous flap plus prosthesis, TRAM flap, free flap). When performed after adequate evaluation and in a technically valid way, BR gives good esthetic and psychological results, has a low incidence of complications or sequelae, and does not affect the natural history of the disease; in particular, BR does not change the percentage of local recurrence or its early diagnosis and allows adequate multidisciplinary treatment.

The continuing importance of adequate surgery for operable breast cancer: significant salvage of node-positive patients without adjuvant chemotherapy.

Five hundred and forty-four patients with primary operable breast cancer were treated by the senior author (JAU) from 1965 to 1970, following a plan of selective surgery involving radical mastectomy (RM), extended radical mastectomy (ERM), and modified radical mastectomy (MRM) applied to appropriate patients. Postoperative radiation therapy was administered to the peripheral regional nodes in 90 percent of node-positive patients. No patient received adjuvant chemotherapy. Significant findings include: • excellent 10-year no-evidence-of-disease (NED) survival following MRM in patients with noninfiltrating cancers (97 percent) and minimal infiltrating cancers (86 percent) • comparable survival (70 percent versus 67 percent alive at 10 years, 63 percent versus 60 percent NED at 10 years) following RM or ERM, in patients with more advanced stages of breast cancer • 10-year survival of 59 percent (50 percent NED) for all patients with axillary node metastases • net local recurrence rate of six percent at 10 years in the 496 patients with infiltrating cancers (44 percent of whom had positive axillary nodes) • internal mammary (IM) node metastases present in 26 percent of ERM patients, with 10-year NED survival of 70 percent when all nodes were negative, 45 percent if only IM nodes were positive, and 35 percent when both axillary and IM nodes were positive. Significant salvage of patients with positive axillary nodes (50 percent NED at 10 years) has been attained through complete excision of the breast and meticulous dissection of the regional nodal depots. Since none of these patients received adjuvant chemotherapy, it is evident that most patients with negative nodes and many with positive nodes do not have systemic disease at the time of primary therapy. Since current methods of adjuvant chemotherapy have improved the five-year survival rates of patients with positive axillary nodes by only 10 percent to 15 percent over that obtained by similar primary therapy in control groups. the current tendency to minimize the importance of adequate primary therapy is irrational and to be condemned. Patients will benefit most when adequate primary therapy with excellent local control is combined with aggressive multidrug adjuvant chemotherapy in appropriate cases.