For the Reviewer # 1 For specific requested changes to the manuscript (point-by-point response):

Transcription

1 Author s response to reviews Title: Successful management of synchronous recurrent breast carcinoma with chronic myelogenous leukemia: A case report Authors: Choukri Elm'hadi (dr.choukrielmhadi@hotmail.com) Mohamed Reda Khmamouche (redastos@hotmail.com) Rachid Tanz (tanz.rachid@gmail.com) Mehdi Toreis (mehdi.toreis@gmail.com) ElMehdi Mahtat (mahtatelmehdi@gmail.com) Mohammed Allaoui (allaoui.m1@gmail.com) Mohammed Oukabli (oukablimohamed@yahoo.fr) Nezha Messaoudi (messaoudi.nezha@yahoo.fr) Hassan Errihani (h_errihani@yahoo.fr) Mohammed Ichou (medichou@yahoo.fr) Version: 1 Date: 22 Jun 2016 Author s response to reviews: Rabat, 15 june, 2016 Dear Editor, I received with great interest your including considerable feedback from reviewers about the manuscript entitled Successful management of synchronous recurrent breast carcinoma with chronic myelogenous leukemia: A case report; Ref: JMCR-D For the Reviewer # 1 For specific requested changes to the manuscript (point-by-point response):

2 1- Spelling mistakes in Title page must be corrected (Example hay riad! Did you mean Hay Riad? Etc) Point response: Spelling mistakes in Title page was corrected, address was modified 2-2-The abstract is too long. Point response: abstract has been reduced 3- Page 5, Line 52 (Cumulative dose were 240mg/m2 for anthracycline and 4800mg/m2 for alkylator) what is the link between this sentence and the discussion of your case report? Point response: In our case, cumulative doses for epirubicin (960 mg/m2) and cyclophosphamide (4800 mg/m2) may explain the occurrence of CML. Modification was added. 4- Please check the English of your manuscript. Point response: For the quality of the English, we reviewed the manuscript with a local linguistic expert speaker to correct mistakes and style. For the Reviewer # 2 For specific requested changes to the manuscript ( point-by-point response): ABSTRACT CASE - 2nd paragraph When the authors state - "at the end of adjuvant treatment "- It should be made clear if this is at the end of chemotherapy or after completion of 5 years of tamoxifen. Point response: this is after completion of 5 years of tamoxifen. Modification was raised - 3rd paragraph Unsure as to what the authors mean by the term 'myelogram' - A myelogram is a radiographic procedure looking at spinal canal. Point response: myelogram was replaced by bone marrow aspiration

3 - Overall abstract needs to be more concise Point response: the abstract was remade INTRODUCTION - Line 5 : Leukemia Chronic Myelogenous leukemia - needs rephrasing - no comma Point response: modification was raised: leukemia chronic myelogenous in survivors of breast carcinoma after adjuvant therapy CASE REPORT - could change wording to 'Case ' Point response: modification was raised - 1st paragraph 1. Line 8: Use chest wall instead of wall Point response: modification was raised 2. Change wording homolateral axillary to ipsilateral axillary Point response: modification was raised 3. Would be prudent to include the blood counts at the time of initial presentation with breast cancer. Point response: modification was raised (Her test results indicated a hemoglobin level of 13.7 g/dl(normal range :12-16 g/dl), a platelet count of 250 x109/l(normal range : x 109/L),a leukocytes count of 7.3 x 10 9 /L (normal range : 4-10 x 109/L) and neutrophils count of 5.1x 109/L(normal range : x 109/L) - 2nd paragraphs 1. hyperleukocytosis at 355 G/ L, platelets and neutrophil counts - count with units are incorrectly represented. Please correct the values to 'count / L' or 'count / mcl' for WBC, Platelet and neutrophils. Hemoglobin values should be in g/dl.

4 Point response: values were corrected(the patient s blood count showed a hyperleukocytosis at 355 x109 /L with a neutrophil count at 152 x109 /L, hemoglobin was at 10.6 g/dl and platelets count of 264 x109/l) 2. Need to include the normal reference range in parenthesis for all values Point response: normal reference range was included DISCUSSION 2nd paragraph a. Authors state association of leukemia with breast cancer is frequently reported - It would lead the readers to believe that leukemia is a frequently reported complication of breast cancer treatment, when in reality the risk is there, but small. It would be important to reveal the statistics here. Point response: This sentence has been corrected (Leukemia is not a usual event in the natural history of breast cancer, though its association with breast cancer therapy has been reported) b. Does the author conclude this as recurrent disease to her original diagnosis. Since the new metastasis had discordant receptor status, does the author think this is a separate cancer altogether. Point response: the authors consider that it is rather a relapse according to literature data that shows a discordance in the status of hormonal receptors and HER2 between the primary and recurrent breast cancer in 37.6% of cases affecting essentially hormonal receptors, frequently in the sense of loss (Houssami N et al., BCRT 2011, Amir E et al., JCO 2011) c. Did the patient have genetic testing because of her young age.? Authors claim an association with TNBC, CML and BRCA. Please substantiate regarding this case. Point response: genetic testing has been proposed for the patient but not realized d. Authors state that the onset of a hematological problem could announce a metastatic disease in solid tumor. This would need further elaboration

5 Point response : This paragraph was improved (Leukocytosis in breast cancer patient initially treated with adjuvant chemotherapy and radiotherapy can reveled chronic myeloid leukemia if a medullary metastatic localization is excluded. It may be accompanied by concomitant visceral metastatic relapse. Optimization of treatment mainly in young patients can prolong survival). For the Reviewer # 3 For specific requested changes to the manuscript ( point-by-point response): The phrase: survival isincreasing revealing frequent relapses and possibility of developing secondarymalignancies.not CLEAR WHAT IT MEANS IMPROVE ENGLISH Point response: this phrase was improved (survival is increasing revealing frequent relapses and the possibility of developing secondary malignancies)n in the case of a Moroccan woman PLEASE CORRECT ENGLISH Point response: this phrase was improved (We reported a case of a Moroccan woman successfully managed for synchronous recurrent breast carcinoma and chronic myelogenous leukemia). to the wall or better chest wall Point response: this phrase was improved Leukocytosis can announce a concomitant metastatic relapse. please better explain: If a metastatic localization is excluded then a diagnosis of chronic myeloid leukaemia should be considered. Point response: this phrase was improved (Leukocytosis in breast cancer patient initially treated with adjuvant chemotherapy and radiotherapy can reveled chronic myeloid leukemia if a medullary metastatic localization is excluded.) Imatinib was ordered as daily concurrently with chemotherapy by docetaxel 100mg/m²every 21 day. PLEASE DETAIL HEMATOLOGICAL TOXICITY IF ANY OF COMBINATION IMATINIB + DOCETAXEL. Point response: there was not limiting hematologic toxicity PLEASE DETAIL IMATINIB DOSAGE USED.

6 Point response: The patient then received a dose of 400mg of Imatinib daily taken as four 100 mg tablets. Leukoerytroblastic reaction can occur in breast cancer, mainly if marrow metastasis occurs. Please include it in differential diagnosis in case of leukocytosis in breast cancer. Point response: differential diagnosis was included (Leukocytosis in monitoring of breast cancer can evoke other diagnoses as extramedullary hematopoiesis, fibrosis, or essentially marrow metastasis with an approximate sensitivity of 75% [16]. Bone marrow carcinomatosisis is typically accompanied by cytopenia and infiltration of the bone marrow by malignant cells. These elements were not present in our patient allowing to exclude this diagnosis). The changes are marked in red in the manuscript. Finally, Dear editor, I hope that this work will find a place in your precious journal.