Multicentre, randomised, open-label, non-inferiority trial comparing the effectiveness and safety of ductal lavage versus oral corticosteroids for idiopathic granulomatous mastitis: a study protocol

IntroductionThe ideal treatment for idiopathic granulomatous mastitis (IGM) remains unclear. In a prospective, single-centre, pilot study, we reported that ductal lavage treatment for non-lactational mastitis patients had a 1-year clinical complete response (cCR) rate of >90%, without any significant adverse events. Thus, in this multicentre, randomised, open-label, non-inferiority trial, we will aim to compare the effectiveness and safety of ductal lavage vs oral corticosteroids as the first-line treatment for patients with IGM.Methods and analysisThe trial will be conducted at the Breast Tumor Center of Sun Yat-sen Memorial Hospital in China and at least at one participating regional centre. We plan to recruit 140 eligible IGM patients who will be randomised into the ductal lavage group or oral corticosteroid group with a 1:1 ratio. The patients in the oral corticosteroid group will receive meprednisone or prednisone for 6 months. The patients in the ductal lavage group will receive ductal lavage and breast massage, as previously reported. All the participants will be followed up at the clinic for 1 year post randomisation. The primary endpoint of this trial will be the 1-year cCR rate, and the secondary endpoints will include the time to cCR, treatment failure rate, relapse rate and protocol compliance rate. The trial was designed to determine whether ductal lavage is non-inferior to oral corticosteroids (1-year cCR rate assumed to be 90%), with a non-inferiority margin of 15%.Ethics and disseminationThe ethics committee of Sun Yat-sen Memorial Hospital at Sun Yat-sen University approved the study (2018-Lun-Shen-Yan-No. 30). The results of the trial will be communicated to the participating primary care practices, published in international journals and presented at international clinical and scientific conferences.Trial registration numberClinicalTrials.gov Registry (NCT03724903); Pre-results.

Association of atypia in ductal lavage and breast cancer risk.

e13040 Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early detection of breast cancer and to provide individualized breast cancer risk assessment will greatly benefit from sampling cellular material from the target tissue. Ductal lavage (DL) is a minimally invasive technique which provides adequate material to detect atypical cells in mammary ducts. However, long term data of the association between atypia from and BC risk are lacking .We studied the prevalence of atypia in DL and its ability to predict BC development in women at risk. Methods: From March 2000 to July 2012 we performed DL in a consecutive series of 348 women with median age of 45 (range 19-74) at increased BC risk based on the following characteristics: 5 yrs Gail model > 1.66% or > 10% probability of BRCA mutation (n = 155), history of contralateral BC (CBC, n = 161), presence of a BRCA pathogenic variant (n = 32). We analyzed the presence of atypical cells in the baseline specimens and observed their evolution during follow-up. Results: The procedure was safe and well tolerated in most women, with pain and disconfort preventing the procedure in 5.4% of subjects. Overall, 126 (36%) women had atypia, with a prevalence of 32%, 39%, and 41% in the Gail, CBC and BRCA groups, respectively (p = 0.38). The overall prevalence of atypia considering all visits was 44% (range 36-51). After a median follow up of 6 years, cumulative BC events were 8% in women without atypia versus 14% in those with atypia (log-rank p = 0.08). In the highest risk groups (CBC and BRCA pathogenic variants), the number of BC events was 16 vs 11 in women with or without atypia (21% vs 10%; log-rank p = 0.05, Cox model adjusted for age p = 0.02). Conclusions: Our findings suggest that cytologic atypia in the fluid obtained by DL may predict the onset of BC in high-risk women. The reversal of atypia in DL as a surrogate biomarker of BC risk reduction warrants investigation.

Ductal lavage cytology in patients with ductal carcinoma in situ (DCIS).

89 Background: Ductal lavage (DL) is a procedure used to obtain epithelial cells from a breast duct for cytologic evaluation. Previous studies have investigated DL as a potential screening procedure for women at high-risk for cancer. The data, however, does not support a significant correlation between lavage cytology and the presence of invasive carcinoma. It is postulated that an invasive cancer causes destruction of the involved ducts which prevents direct sampling of the malignant intraductal cells. Because ductal carcinoma in-situ (DCIS) does not disrupt the breast ductal structure, DL may yield a more representative cytologic sample in patients with DCIS. Methods: Ductal lavage was performed in the affected breast of 32 women undergoing mastectomy with preoperative diagnosis of DCIS. The lavage procedure was done in the operating room after induction of general anesthesia by cannulating a duct yielding fluid on the nipple and instilling saline which was then aspirated and sent for cytologic evaluation. A cytopathologist classified each sample as insufficient cellular quantity, benign, mild atypia, marked atypia, or malignant. Results: A successful lavage was obtained from 22 (69%) of 32 women undergoing DL in the operating room. Of these 22 cytology samples; 4(18%) had an insufficient cellular quantity, 4 (18%) had mild atypia, 6 (27%) had marked atypia, and 8 (36%) had malignant cells. Twenty one of these 22 women had DCIS in the surgical mastectomy specimen. Seven (32%) patients were found to have invasive ductal cancer in addition to DCIS on final pathology. Conclusions: Our results show that DL reveals markedly atypical or malignant cytology in 64% of patients with DCIS who underwent a successful lavage procedure. As an office procedure, DL may have the ability to obtain viable ductal carcinoma cells repeatedly over time in the same patient. Thus, DL may have an important role in patients with DCIS who are involved in window trial studies investigating response to medical treatments prior to surgical intervention. Further studies to evaluate the reproducibility of the ductal lavage results in patients with DCIS are needed to confirm these findings.

Optimization of a cytologic and bacteriological assessment of a pathological secret at chronic duktoforit at women with a mastopatiya

The given paper describes high efficiency of detecting chronic inflammation of the mammary ducts (96.2 %) in women with mastopathy by enlargement of cellular composition by means of optimization for the technique of intraductal secretion sampling with the help of mammary duct lavage in comparison with exfoliative method (touch smear) (24.8 %, p < 0.001). The technique of sampling with the help of mammary duct lavage increases detectability of pathogenic flora (82.7 %, p < 0.001) by 2.6 times in comparison with exfoliative method (31.6 %, p < 0.001). It has been established that preliminary sanitation of secerning ducts of a mammary gland prior to ductography increases by 10 times information value for detecting distorting inflammation of the mammary ducts (24.7 %) in comparison with contrast mammography without preliminary ductal lavage (2.5 %, p < 0.001).