Risk and incidence of breast cancer in transgender individuals: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk of developing breast cancer in transgender individuals [male-to-female (MtF) or female-to-male (FtM)] is still inadequately quantified. We aimed to evaluate the impact of breast cancer in this population. METHODS: We conducted a systematic literature search and review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines through the PUBMED and SCOPUS databases. We identified six cohort studies (for both populations) plus 35 case reports. Incidence and breast cancer risk quantification were the main outcomes considered. RESULTS: FtM individuals had a higher risk of developing breast cancer in comparison to cisgender men [standardized incidence ratio (SIR) = 63.4; 95% confidence interval (CI), 32.2-124.9] but a lower risk than cisgender women (SIR = 0.42; 95% CI, 0.07-2.41). Similarly, MtF individuals were at higher risk of developing breast cancer in comparison to cisgender men (SIR = 22.5; 95% CI, 5.54-91.8) and at lower risk than cisgender women (SIR = 0.30; 95% CI, 0.22-0.42). CONCLUSION: In this systematic study and meta-analysis, we identified that FtM and MtF individuals are at substantially higher risk of developing breast cancer in comparison to cisgender men, though at lower risk than cisgender women. These individuals, in the absence of defined guidelines for breast cancer prevention, should periodically undergo breast or chest examinations.

Diagnostic performance of image-guided vacuum-assisted breast biopsy after neoadjuvant therapy for breast cancer: prospective pilot study.

BACKGROUND: Image-guided vacuum-assisted breast biopsy (VABB) of the tumour bed, performed after neoadjuvant therapy, is increasingly being used to assess residual cancer and to potentially identify to identify pathological complete response (pCR). In this study, the accuracy of preoperative VABB specimens was assessed and compared with surgical specimens in patients with triple-negative or human epidermal growth factor receptor 2 (HER2)-positive invasive ductal breast cancer after neoadjuvant therapy. As a secondary endpoint, the performance of contrast-enhanced MRI of the breast and PET-CT for response prediction was assessed. METHODS: This single-institution prospective pilot study enrolled patients from April 2018 to April 2021 with a complete response on imaging (iCR) who subsequently underwent VABB before surgery. Those with a pCR at VABB were included in the primary analysis of the accuracy of VABB. The performance of imaging (MRI and PET-CT) was analysed for prediction of a pCR considering both patients with an iCR and those with residual disease at postneoadjuvant therapy imaging. RESULTS: Twenty patients were included in the primary analysis. The median age was 44 (range 35-51) years. At surgery, 18 of 20 patients showed a complete response (accuracy 90 (95 per cent exact c.i. 68 to 99) per cent). Only two patients showed residual ductal intraepithelial neoplasia of grade 2 and 3 respectively. In the secondary analysis, accuracy was similar for MRI and PET-CT (77 versus 78 per cent; P = 0.76). CONCLUSION: VABB in patients with an iCR might be a promising method to select patients for de-escalation of surgical treatment in triple-negative or HER2-positive breast cancer. The present results support such an approach and should inform the design of future trials on de-escalation of surgery.

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study.

BACKGROUND: Ribociclib plus letrozole demonstrated manageable safety and efficacy profiles in hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) in the Phase 3b CompLEEment-1 trial. OBJECTIVE: To evaluate the safety and efficacy of ribociclib plus letrozole in the Italian subpopulation with HR+, HER2- ABC from the CompLEEment-1 trial. PATIENTS AND METHODS: Patients with HR+, HER2- ABC received ribociclib (600 mg/day, 3 weeks on/1 week off) plus letrozole (2.5 mg/day) while men and premenopausal women additionally received goserelin. Patients were allowed with ≤ 1 line of prior chemotherapy and an Eastern Cooperative Oncology Group performance status of ≤ 2. The primary outcome included safety and tolerability. RESULTS: Of the 554 Italian patients, 246 (44.4 %) patients completed treatment. The reasons for treatment discontinuation included progressive disease (PD; 36.6 %), adverse events (AEs; 11.9 %), and death (1.6 %). All-grade AEs and grade ≥ 3 AEs occurred in 98.9 % and 77.8 % patients, respectively. The most common treatment-related AEs were neutropenia (73.6 %), followed by leukopenia (32.1 %), and nausea (25.3 %). The overall response rate was 28.2 % (95 % confidence interval [CI], 24.4-32.1); clinical benefit rate was 71.7 % (95 % CI, 67.7-75.4); and median time to progression was 26.7 months (95 % CI, 24.8-non-estimable). Health-related quality of life scores were maintained during treatment. CONCLUSION: The safety and efficacy profiles of ribociclib plus letrozole in the Italian subpopulation was found to be consistent with the CompLEEment-1 global population result, MONALEESA-2, and MONALEESA-7 outcomes, which reaffirm ribociclib plus letrozole as the frontline treatment option in patients with HR+, HER2- ABC. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT02941926 (30 November 2016).

Social Media Listening to Understand the Lived Experience of Individuals in Europe With Metastatic Breast Cancer: A Systematic Search and Content Analysis Study.

Background: Despite a wealth of real-world data on metastatic breast cancer (mBC), insights into the lived experience are lacking. This study aimed to explore how the lived experience of mBC is described on social media. Methods: A predefined search string identified posts relevant to the lived experience of mBC from Twitter, patient forums, and blogs across 14 European countries. The final data set was analyzed using content analysis. Results: A total of 76,456 conversations were identified between November 1, 2018, and November 30, 2020. Twitter was the most commonly used social media platform across all 76,456 conversations from the raw data set (n = 61,165; 80%). Automated and manual relevancy checks followed by a final random sampling filter identified 820 conversations for content analysis. The majority of data from the raw data set was generated from the United Kingdom (n = 31,346; 41%). From this final data set, 61% of posts were authored by patients, 15% by friends and/or family members of patients, and 14% by caregivers. A total of 686 conversations described the patient journey (n = 686/820; 84%); 64% of these (n = 439) concerned breast cancer treatment, with approximately 40% of discussions regarding diagnosis and tests (n = 274/686) and less than 20% of discussions surrounding disease management (n = 123/686; 18%). Key themes relating to a lack of effective treatment, prolonged survival and associated quality of life, debilitating consequences of side effects, and the social impacts of living with mBC were identified. Conclusions: The findings from this study provided an insight into the lived experience of mBC. While retrospective data collection inherently limits the amount of demographic or clinical information that can be obtained from the population sample, social media listening studies offer training to healthcare professionals in communication, the importance of quality of life, organization of healthcare, and even the design of clinical trials. As new targeted therapies are gradually incorporated into clinical practice, innovative technologies, such as social media listening, have the potential to support regulatory procedures and drug toxicity monitoring, as well as provide the patient voice in the regulation of new and existing medicines.

Pegylated Liposomal Doxorubicin (Caelyx®) as Adjuvant Treatment in Early-Stage Luminal B-like Breast Cancer: A Feasibility Phase II Trial.

BACKGROUND: Adjuvant chemotherapy for Luminal B-like breast cancers usually includes anthracycline-based regimens. However, some patients are reluctant to receive chemotherapy because of side-effects, especially alopecia, and ask for a "less intensive" or personalized approach. PATIENTS AND METHODS: We conducted a phase II feasibility trial to evaluate pegylated liposomal doxorubicin (PLD, Caelyx®) as adjuvant chemotherapy. Patients who received surgery for pT1-3, any N, and luminal B-like early-stage breast cancer (EBC) candidates for adjuvant chemotherapy were included. PLD was administered intravenously at 20 mg/m2 biweekly for eight courses. Endocrine therapy was given according to menopausal status. Trastuzumab was administered in HER2-positive disease. The primary endpoint was to evaluate the feasibility of this regimen, defined as the ability of a patient to achieve a relative dose intensity (RDI) of at least 85% of the eight cycles of treatment. Secondary endpoints included adverse events (AEs), tolerability, breast cancer-free survival, disease-free survival, and overall survival. RESULTS: From March 2016 to July 2018, 63 patients were included in the trial. Median age was 49 years (range: 33-76), with mostly pre- and peri-menopausal (65%) and stage I-II (94%). Only 5% of patients had HER2-positive EBC. Median RDI was 100% (range: 12.5-100%; interquartile range, IQR: 87.5-100%). The proportion of patients meeting the primary endpoint was 84% (95% confidence interval, CI: 73-92%). Overall, 55 out of 63 enrolled patients completed treatment (87%, 95% CI: 77-94%). Most common AEs were palmar-plantar erythrodysesthesia (12.2%), fatigue (10.4%), and mucositis (8.5%). Only 13% of patients had G3 AEs. None had alopecia. After a median follow-up of 3.9 years (range: 0.3-4.7) two distant events were observed, and all patients were alive at the date of last visit. CONCLUSIONS: The trial successfully met its primary endpoint: the regimen was feasible and well tolerated and could be considered for further evaluation as a treatment option for patients with contraindications to standard anthracyclines or requiring a personalized, less intensive approach.

Fulvestrant in Combination with CDK4/6 Inhibitors for HER2- Metastatic Breast Cancers: Current Perspectives.

The development of CDK 4/6 inhibitors has dramatically changed the therapeutic management of hormone receptor-positive (HR+) and HER2 negative metastatic breast cancer (MBC). In combination with fulvestrant, palbociclib, ribociclib and abemaciclib have each been approved for HR+/HER2- MBC following the results of randomized Phase III studies (PALOMA-3, MONALEESA-3, MONARCH-2) and shown a significant advantage in PFS. Data from clinical trials support the combination with aromatase inhibitors in the first line setting and with fulvestrant in the second line. Each agent is well tolerated, and most of the toxicities observed with this class of drugs are generally easily manageable and free from particular complications. The latest evidence from MONARCH-2 and MONALEESA-3 trials shows benefits in terms of overall survival (OS), suggesting an option of using fulvestrant in combination with CDK 4/6 inhibitors in the first line setting. Additional research is needed to determine optimal treatment sequencing, understand the mechanisms of resistance, and develop novel therapeutic strategies to overcome clinical resistance and further improve the outcomes of patients with HR+/HER- MBC. Key questions in the field include the further impact on progression-free survival, overall survival, and the role of continuing CDK 4/6 blockade beyond progression. The purpose of this review is to describe the clinical relevance of fulvestrant in combination with CDK 4/6 inhibitors in HR+/HER2- MBC patients, as well as to discuss the current controversies and evolving research areas.

Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a distressing side effect of cancer therapy. The trial aimed to assess feasibility and effectiveness of scalp-cooling system DigniCap® to prevent CIA in primary breast cancer patients receiving an anthracycline containing adjuvant chemotherapy (CT). METHODS: Hair loss (HL) was evaluated by patient self-assessment and by the physician according to the Dean's scale at baseline and after each cycle of CT. The primary efficacy endpoint was the patient self-assessment HL score evaluated at least 3 weeks after completing CT. A Dean's scale score of 0-2 (i.e. HL ≤50%) was considered a success. RESULTS: From July 2014 to November 2016, 139 consecutive breast cancer patients were enrolled and received at least one treatment with scalp cooling. Fifty-six out of 131 evaluated patients successfully prevented HL (43%, 95% CI: 34-51%). Twenty-four patients (32%) discontinued the scalp cooling because of alopecia or scalp-cooling related AE, three patients had missing information on CIA, and 48 patients (64%) had a HL greater than 50% after CT. No serious AEs were reported. CONCLUSIONS: DigniCap® System resulted as a promising medical device to be safely integrated in supportive care of early breast cancer patients. Longer follow-up is needed to assess long-term safety and feasibility. CLINICAL TRIAL REGISTRATION NUMBER: NCT03712696.

Metronomic Chemotherapy for First-Line Treatment of Metastatic Triple-Negative Breast Cancer: A Phase II Trial.

BACKGROUND: Few data are available on the benefit of metronomic cyclophosphamide, capecitabine, and vinorelbine as first-line therapy in patients with metastatic triple-negative breast cancer. METHODS: This phase II study assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine 40 mg orally 3 times a week, cyclophosphamide 50 mg daily, and capecitabine 500 mg 3 times a day (VEX regimen) in untreated metastatic triple-negative breast cancer patients. The biopsy of the metastatic site had to be triple-negative, independent of the hormone receptor expression of the primary tumor. The primary endpoint was time to progression (TTP). Secondary endpoints included assessment of safety and clinical benefit (objective response rate plus stable disease rate at ≥24 weeks). RESULTS: 25 patients were included, and 22 were evaluable for both efficacy and toxicities (median age, 66 years). Median TTP was 6.4 months (95% confidence interval 3.6-12.6). The most common grade 1-2 toxicities were nausea, diarrhea, leuko-/neutropenia, and reversible liver enzyme alteration. Grade 3 events included hand and foot syndrome (9%). CONCLUSION: The VEX regimen demonstrated activity and was relatively well tolerated when given as first-line therapy in selected metastatic breast cancer patients with triple-negative disease.

Phase II Trial of Bevacizumab Plus Weekly Paclitaxel, Carboplatin, and Metronomic Cyclophosphamide With or Without Trastuzumab and Endocrine Therapy as Preoperative Treatment of Inflammatory Breast Cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and highly aggressive disease. A neoadjuvant regimen with chemotherapy and an antiangiogenic strategy was investigated. PATIENTS AND METHODS: Patients with primary or recurrent IBC who were candidates for neoadjuvant treatment received weekly carboplatin and paclitaxel plus bevacizumab every 3 weeks and oral metronomic cyclophosphamide for 6 months. Trastuzumab was added for patients with HER2+ tumors and endocrine therapy was added for patients with estrogen receptor and/or progesterone receptor ≥ 10% tumors. Oral metronomic capecitabine and cyclophosphamide was continued for 6 months after surgery in those patients with a response. The primary efficacy endpoints were pathologic complete remission (pCR) and the objective response. RESULTS: From July 2010 to December 2013, 34 patients with IBC were included. The surrogate intrinsic tumor subtypes were as follows: luminal B-like (HER2-), 10 (29%); luminal B-like (HER2+), 8 (24%); HER2+ (nonluminal), 6 (18%); and triple negative, 10 (29%). An objective response was obtained in 30 patients (88%; 95% confidence interval, 73%-97%) and a pCR in 10 patients (29%; 95% confidence interval, 15%-48%). The proportion of pCR was significantly greater in the patients with HER2+ tumors (57%) than in patients with triple-negative (20%) or luminal B-like (HER2-) tumors (0%; P = .019). After a median follow-up of 4.4 years, the 5-year disease-free survival and overall survival was 58% and 72%, respectively. The achievement of pCR was associated with longer disease-free (P = .12) and overall (P = .029) survival. CONCLUSION: In patients with IBC, neoadjuvant treatment with the investigated regimen was successful and well tolerated. Further studies evaluating the potential benefit of an antiangiogenic strategy in this setting are awaited.

Safety and efficacy study of metronomic vinorelbine, cyclophosphamide plus capecitabine in metastatic breast cancer: A phase II trial.

In a phase II study we assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine, cyclophosphamide capecitabine in patients with metastatic breast cancer, either as first-line (naïve group) or second-line or greater therapy (pre-treated group). Eligible patients had histologically or cytologically proven, hormone-receptor positive metastatic breast cancer. The primary end point was median time to progression (TTP). A total of 43 patients in the naïve group and 65 in the pre-treated group were enrolled. The median TTP was 25.1 months in the naïve group and 11.2 months in the pre-treated group. The most frequently reported grade 2 treatment-related adverse events were leukopenia and hand and foot syndrome. Metronomic combination of cyclophosphamide, capecitabine and vinorelbine showed significant activity and good tolerability in patients hormonal receptor positive, metastatic breast cancer patients.

Long-lasting control with eribulin in a taxane pretreated metastatic breast cancer patient.

Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Moreover, many chemotherapeutic agents need to be interrupted due to toxicity. Here we report an extremely long duration of chemotherapy with eribulin (11 courses) in a taxane-pretreated metastatic breast cancer patient. Therapy was well tolerated with no worsening of pre-existing neuropathy, achieving excellent outcomes and a good quality of life. This report adds to the pool of knowledge regarding the use of this important new metastatic breast cancer chemotherapeutic agent.

Prognostic relevance of peritumoral vascular invasion in immunohistochemically defined subtypes of node-positive breast cancer.

Prognostic factors to better identify subcategories of node-positive breast cancer patients candidate to adjuvant chemotherapy are needed. The prognostic significance of the extent of peritumoral vascular invasion (PVI) in patients with positive axillary nodes is a matter of controversy. No data are available on the role of PVI within immunohistochemically defined subtypes. 3,729 consecutive patients with primary invasive breast cancer and positive axillary nodes were operated and referred for interdisciplinary evaluation from April 1997 to December 2005. Patients were classified as Luminal A, Luminal B(HER2 negative), Luminal B(HER2 positive), Triple Negative and HER-2 positive. The distribution of PVI was as follows: absent 2,010 (54 %), moderate/focal 963 (142 + 821) (26 %), and extensive 756 (20 %). Patients with extensive PVI were more likely to be Luminal B(HER2 negative) (49.3 %), younger (35-50 years), to have larger tumors (>pT2) with higher grade, a higher extent of node involvement (>4 nodes) and higher proliferative index, compared with patients with absence or moderate/focal PVI (p < 0.0001). In the multivariate analysis, extensive PVI (vs. absent) was correlated with a significant higher risk of local recurrence (HR 1.42, 95 %CI, 1.03-1.95, p = 0.0301). The immunohistochemically defined Luminal A-like subtype had a significant better outcome in terms of DFS, OS and reduced incidence of distant metastases when compared with the other subtypes. The occurrence of extensive PVI correlates with an increased risk of local recurrence. Luminal A tumors, classified according to the most recent St. Gallen recommendations, had an excellent outcome irrespective to the occurrence of extensive PVI or lymph node metastases and might be a good candidate to personalized adjuvant treatments.

Outcome of male breast cancer: a matched single-institution series.

BACKGROUND: Breast cancer occurs rarely in men, accounting for approximately 1% of all breast carcinomas. Data on prognosis principally derive from retrospective studies and from extrapolation of female breast cancer series. PATIENTS AND METHODS: A total of 99 men with invasive breast cancer were matched with 198 women with breast cancer who had surgery at the same institution from 1999 to 2010. Matching variables were year of surgery, age, primary tumor size, nodal involvement, hormone receptor status, status of HER2 (human epidermal growth factor receptor 2 [ERBB2]), Ki-67, and grade. Median follow-up was 8.6 years. RESULTS: Disease-free survival (DFS) was significantly poorer in the men (10-year DFS, 51.7% vs. 66.5%; hazard ratio [HR], 1.79; 95% CI, 1.19-2.68; P = .004). Similar results were observed for overall survival (OS) (10-year OS, 70.7% vs. 84.2%; HR, 1.79; 95% CI, 1.01-3.15; P = .043). The cumulative incidence of death for causes not related to the primary breast cancer was significantly higher for men than for women (HR, 2.87; 95% CI, 1.58-5.22; P = .001), whereas the breast cancer-specific survival (BCSS) was similar between the 2 groups (10-year BCSS, 81.5% vs. 88%; HR, 1.27; 95% CI, 0.62-2.59; P = .517). CONCLUSION: This comparative series found that men with breast cancer had a poorer DFS and OS when compared with women. The men also had a higher risk of contralateral tumors and second primaries. Appropriate counseling, surveillance, and prevention are recommended to improve survival for these individuals.

Pathological features and survival outcomes of very young patients with early breast cancer: how much is "very young"?

We collected information on 497 consecutive breast cancer patients aged less than 35 years operated at the European Institute of Oncology. The main aim of the study is to compare biological and clinical features dividing the population by age: <25 years, 25-29 and 30-34 years old. Pattern of recurrence and survival were also analyzed. Patients aged <25 years had 81.8% poorly differentiated tumors compared with 66.7% and 56.5% in the 25-29 and 30-34 groups, respectively; no other significant difference were found in the distribution of clinical and immunohistochemical features The distribution of Luminal A and B, Triple Negative and HER2 subtypes (immunohistochemically defined) was not statistically different among the three age groups. No difference was found in the incidence of loco-regional relapses, distant metastases, disease-free survival (p = 0.79) and overall survival (p = 0.99) between the three age groups. This latter findings was confirmed using age as a continuous variable assuming a linear association between age and the outcomes considered, too. In conclusion, our data indicate that the group of patients with breast cancer below 35 years is essentially a homogenous group when classical clinical and immunohistochemical features were considered.

Immunohistochemically defined subtypes and outcome of apocrine breast cancer.

BACKGROUND: Conflicting data are available in the literature on the outcome of invasive apocrine carcinoma (IAC), possibly related to a heterogeneous classification of these tumors. PATIENTS AND METHODS: A series of 6899 consecutive patients with invasive ductal carcinoma (IDC) not otherwise specified and 72 patients with immunohistochemically defined IAC who received surgery at the European Institute of Oncology between 1997 and 2005 were included. We then explored patterns of recurrence of IAC according to 2 immunohistochemically defined tumor subtypes: pure apocrine carcinoma (estrogen [ER] and progesterone [PgR] receptor negative, and AR positive) and apocrine-like carcinoma (ER or PgR positive and AR negative). RESULTS: The diagnosis of pure apocrine carcinoma was correlated with a worse outcome in terms of DFS (hazard ratio [HR] 1.7; 95% confidence interval [CI], 1.01-2.86; P = .0010) if compared with IDC, whereas IDC and apocrine-like breast cancers showed a similar outcome in terms of DFS and overall survival. Patients with pure apocrine carcinoma had an increased risk in contralateral breast cancer (HR, 4.12; 95% CI, 1.22-14; P = .02). CONCLUSION: Pure apocrine carcinoma represents a distinct subtype of breast cancer with a significantly worse DFS as compared with IDC. AR determination might have an important prognostic implication in IAC. Moreover, AR-targeted therapy should be further explored within these tumors.

Immunohistochemically defined subtypes and outcome in occult breast carcinoma with axillary presentation.

The aim of this study is to evaluate the outcome of occult breast cancer (OBC) in patients with axillary presentation overall and according to the immunohistochemically defined tumour subtypes. We reviewed information on 15,490 consecutive primary breast cancer patients, who underwent surgery at the European institute of oncology between September 1997 and December 2008. Patients with OBC were compared with an equal number of patients with small invasive breast carcinomas (pT1) observed at the same institution during the same period, matched for year of surgery, age, nodal status and biological features. Eighty patients with OBC (study group) and 80 patients with early breast cancer (control group) were identified. There was no significant difference in the disease-free survival (5 years DFS 66 vs. 68% P = 0.91) and the overall survival (5 years OS 80 and 86% P = 0.99) between the OBC and control groups. A statistically significant worse outcome was observed within the group of OBC for patients with more than four involved lymph nodes and with triple negative tumours. The outcome of OBC patients is comparable with that of matched patients with small sized breast cancer. High risk of relapse and death was observed in OBC patients with triple negative tumours and extensive nodal involvement.

Pegylated liposomal doxorubicin in combination with low-dose metronomic cyclophosphamide as preoperative treatment for patients with locally advanced breast cancer.

AIM: To evaluate the role of pegylated liposomal doxorubicin with low-dose metronomic cyclophosphamide as primary systemic treatment in locally advanced breast cancer. PATIENTS AND METHODS: The activity and safety of intravenous pegylated liposomal doxorubicin 20 mg sqm(-1) biweekly for eight courses in combination with metronomic cyclophosphamide 50 mg day(-1) orally were evaluated in 29 patients with locally advanced breast cancer who were not suitable to receive a standard chemotherapy due to age or co-morbidities or who asked for a regimen with low incidence of toxic effects irrespective of age. RESULTS: The rate of breast-conserving surgery was 44.8%. Eighteen patients (62.1%) achieved a partial response (including one pathological complete response), 10 (34.5%) a stable disease and one patient experienced a progressive disease. Treatment was well tolerated, with no grade 4 toxicities, and with grade 3 skin toxicity in three patients and hand-foot syndrome in four patients. CONCLUSION: The regimen was well tolerated but with limited activity in the preoperative setting. Other options (e.g., endocrine therapy in estrogen receptor -positive disease) should be considered in locally advanced breast cancer patients who are not suitable to receive a standard chemotherapy.