• Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 4  |  Issue : 4  |  Page : 89-94

Therapy-induced histopathological changes in breast cancers: The changing role of pathology in breast cancer diagnosis and treatment


1 Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Mangalore, Karnataka, India
2 Department of Pediatrics and Neonatology, McMaster University, Hamilton, Ontario, Canada
3 Department of Pedodontics, Saraswati-Dhanwantari Dental College and Hospital and Post-Graduate Research Institute, Parbhani, Maharashtra, India
4 Department of Oral Medicine and Radiology, Saraswati-Dhanwantari Dental College and Hospital and Post-Graduate Research Institute, Parbhani, Maharashtra, India
5 Department of Oral Medicine and Radiology, Government Dental College and Research Institute, Bangalore, Karnataka, India

Date of Submission13-Jul-2018
Date of Acceptance21-Aug-2018
Date of Web Publication31-Aug-2018

Correspondence Address:
Dr. Abhishek Singh Nayyar
Department of Oral Medicine and Radiology, Saraswati-Dhanwantari Dental College and Hospital and Post-Graduate Research Institute, Parbhani 431401, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ctm.ctm_23_18

Rights and Permissions
  Abstract 


Aim: Breast cancer therapy causes morphological alterations in the cancerous as well as the surrounding healthy tissue. The histopathological interpretation in such cases, thus, requires a thorough knowledge of the cytological and stromal changes rendered by the therapy during and posttherapy. The aim of the present study was to evaluate such cytological and stromal changes rendered by the therapy in breast cancer cases.
Methods: The present study was a combined retrospective and prospective study, wherein clinical and histopathological details were collected from a total of 39 cases of breast carcinoma before and posttherapy, and the changes induced by the therapy were correlated.
Results: Stage II breast carcinoma was found to be the most predominant stage, while invasive ductal carcinoma-not otherwise specified (IDC-NOS) of tumor was the most common histologic type both before (94.87%) and after (76.92%) therapy. Pathologic complete response (pCR) was observed in 18% of the cases while 15% showed pathologic partial response (pPR) and 66.7% cases had a stable disease. Intracellular changes commonly noted after chemotherapy included nuclear enlargement, hyperchromasia, and increased nuclear: cytoplasmic ratio while predominant stromal changes included necrosis (74.4%), fibrosis (64.1%), and desmoplasia (59%).
Conclusion: Breast cancer therapy causes morphological alterations in the cancerous as well as the surrounding healthy tissue. The histopathological interpretation in such cases, thus, requires a thorough knowledge of the cytological and stromal changes rendered by the therapy.

Keywords: Breast cancer diagnosis and treatment, breast cancers, neoadjuvant chemotherapy, therapy-induced histopathological changes


How to cite this article:
Sheereen S, Lobo FD, Patel W, Sheereen S, Nayyar AS, Khan M. Therapy-induced histopathological changes in breast cancers: The changing role of pathology in breast cancer diagnosis and treatment. Cancer Transl Med 2018;4:89-94

How to cite this URL:
Sheereen S, Lobo FD, Patel W, Sheereen S, Nayyar AS, Khan M. Therapy-induced histopathological changes in breast cancers: The changing role of pathology in breast cancer diagnosis and treatment. Cancer Transl Med [serial online] 2018 [cited 2020 Apr 4];4:89-94. Available from: http://www.cancertm.com/text.asp?2018/4/4/89/240294




  Introduction Top


Breast cancer is the most common cancer diagnosed in women and is the second leading cause of death in women globally.[1] Even though most cases occur over the age of 50 years, it is uncommon in younger women.[1],[2] Breast cancer is not a single disease and comprises several entities ranging from ductal carcinoma in situ (DCIS) to a widespread metastatic disease.[3] Clinical presentation and investigations such as mammography and fine-needle aspiration cytology (FNAC) often help in the diagnosis of breast cancers. However, histopathological examination remains the better predictor for an accurate diagnosis of breast cancers. In addition, immunohistochemical markers aid in classification and are often used to guide the therapy of the disease process. Therapy and prognosis depend on the various clinical and histopathological factors including tumor size, type of tumor, hormonal receptor status, the type of therapy provided, and most significantly, at what stage the cancer is diagnosed. Due to extensive advances made in the field of oncology, various modes of therapy of breast cancers are available at present including surgery, radiotherapy, chemotherapy, and more specifically, targeted hormonal and tumor receptors therapy. Surgery which may include mastectomy or breast-conserving surgery (lumpectomy), still, remains the prime modality of therapy for most of the operable breast cancers. Hormonal therapy can be a significant addition along with surgery or chemotherapy, especially in patients who are estrogen receptor (ER) and/or progesterone receptor (PR) +ve. Hormonal receptor status can, thus, significantly alter the modality of therapy provided and may have better outcomes. In advanced disease, before surgery, radiation therapy is used to reduce the size of the tumor. In early breast cancers, to facilitate breast conservation, chemotherapy is more commonly used both as a neoadjuvant chemotherapy and/or postoperative chemotherapy.[4] In the modern era, increased number of neoadjuvant therapy-induced surgical resection specimens of tumors are being received in histopathological evaluation laboratories. The pathologist evaluates the residual tumor both in the breast and lymph nodes. Assessment of the therapy-induced morphological changes seen at the cytological and stromal levels, thus, requires a thorough knowledge of the possible cytological and stromal changes rendered by the therapy. The aim of the present study was to evaluate such cytological and stromal changes rendered by the therapy in breast cancer cases. This ensures the role of the pathologists in the correct diagnosis as well as grading of the tumor with a correct histopathological interpretation for an effective and planned regimen of the therapy increasing prognosis and chances of survival of the affected patients rendering better clinical outcome and an effective patient care.


  Methods Top


The present study was a combined retrospective and prospective study conducted over a period of 1 year from January 2017 to December 2017. Clinical and histopathological details were collected from a total of 39 cases of breast carcinoma before and posttherapy and the changes induced by the therapy were correlated. All the patients who had been diagnosed with Stage II and III (T1-T4, N0-2, and M0) carcinoma breast were included in the study while patients already treated with chemo-or hormonal therapy and patients who only underwent surgery without chemo-or hormonal therapy and wherein biopsy samples were found to be inadequate were excluded from the study. The patients included in the study were informed about the details of the study and written informed consent was obtained. The study protocol was approved by the Institutional Ethics Committee governing the protection of privacy of the participants enrolled for the study. A detailed case history was taken including chief complaint, history of presenting illness, and medical and personal histories. A thorough clinical examination, including systemic and regional examination, was done. Treatment planning was done based on the final diagnosis arrived after the necessary investigations. The required clinical data of the patients, their lymph node status, and investigation reports (mammography, FNAC, biopsy, ER/PR status, and Her2/neu status) was collected before the start of the planned therapy. The initial biopsies were subjected to routine formalin fixation and paraffin processing with microscopic analysis on hematoxylin and eosin stained sections supplemented by special stains including immunohistochemistry to decide the histological types and grades of the tumor and hormonal status. Subsequently, when the patients had received 2-6 cycles of chemotherapy or hormonal therapy, histopathological (gross and microscopic) and immunohistochemical examination was performed and all the details pertaining to microscopic and clinical findings along with immunohistochemical findings were recorded and the changes induced by therapy were correlated.

Statistical analysis

Statistical analysis was done using IBM SPSS statistics 17 (Chicago, USA). The data were analyzed by proportions, tables, and graphs while various morphological features were analyzed for their frequency and were compared with the final diagnosis using Chi-square value (χ2), paired t-test, and Fischer's test. P < 0.05 was considered to be statistically significant, while P < 0.001 was considered as highly significant.


  Results Top


The study consisted of 39 breast carcinoma cases. The present study revealed swelling in the affected breast as the most common chief complaint while mastalgia (38.5%), discharge from the nipple, and ulcer were the other common complaints. The right breast was more commonly involved (66.7%) and upper and outer quadrant was the most common location of the tumor (74.4%) followed by upper and inner quadrant (8%). In 13% of the cases, more than one quadrant was involved. Majority of the cases (69%) in the present study received 4 to 6 cycles of neoadjuvant chemotherapy, while 31% of cases received more than 6 cycles of chemotherapy. AC regimen (doxorubicin, cyclophosphamide followed by paclitaxel) was the most common (26 cases, 64.1%) chemotherapy regimen received. The second most common (8 cases, 20.5%) regimen received was CAF (cyclophosphamide, doxorubicin, and 5-fluorouracil) followed by CEF regimen (cyclophosphamide, epirubicin, and 5-fluorouracil) (6 cases, 15.38%). The mean size of the tumor before induction of chemotherapy was found to be 3.75 cm while after chemotherapy was 1.75 cm (P < 0.001). The size of the tumor decreased consistently after neoadjuvant chemotherapy. Stage II breast carcinoma was found to be the most predominant (61.5%) stage with Stage IIA accounting for up to 38.5% of the cases. 23% of the cases were found to be in Stage III. It was observed that younger women had an aggressive breast cancer with Stage III as the predominant stage noted. Infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) [Figure 1], [Figure 2], [Figure 3] was the most common histologic type both before (94.87%) and after (76.92%) therapy. One case of lobular carcinoma and one case of metaplastic carcinoma [Figure 4] was also found. Thirty-two of the 39 tumors changed grade to either a higher or lower grade (P < 0.05). On histopathological examination, pathologic complete response (pCR) [Figure 5] and [Figure 6] was observed in 18% of the cases while 15% showed pathologic partial response (pPR) and 66.7% cases had a stable disease with no progression of disease [Table 1]. The fundamental manifestation of the effect of therapy was an obvious decrease in tumor cellularity. Intracellular changes commonly noted after chemotherapy included nuclear enlargement, hyperchromasia, and increased nuclear: cytoplasmic (N:C) ratio which were found in up to 85% of the cases followed by the presence of prominent nucleoli and karyorrhexis/karyolysis noted in 70%–75% of the cases [Table 2]. The predominant stromal changes seen posttherapy were necrosis (74.4%), fibrosis (64.1%) [Figures 1c, 2, 3, 5, and 6], desmoplasia (59%), and degenerative changes (33.3%). Other significant stromal changes included mucinous changes, hyalinization of walls of blood vessels [Figure 1]c, neoangiogenesis, calcific deposits [Figure 2], loss of cellular architecture and appearance of chronic inflammatory cell infiltration [Figures 5b-c and 6], and hemosiderin-laden macrophages [Figure 3], giant cells, and histiocytes [Table 3].
Figure 1: Infiltrating Ductal Carcinoma-Not otherwise specified: Post-therapy evaluation of tumor: Residual tumor cells in lymph nodal tissue (H and E, a: ×200, b: ×400); Lymph nodal tissue showing residual tumor cells with areas of fibrosis and hyalinization (H and E, c: ×100)

Click here to view
Figure 2: Infiltrating Ductal Carcinoma-Not otherwise specified: Post-therapy evaluation of tumor: Residual tumor cells showing areas of fibrosis and calcification (H and E, a: ×100, b: ×200, c: ×200)

Click here to view
Figure 3: Infiltrating Ductal Carcinoma-Not otherwise specified: Post-therapy evaluation of tumor: Residual tumor cells showing hemosiderin laden macrophages along with areas of fibrosis (H and E, a: ×40, b: ×100, c: ×200)

Click here to view
Figure 4: Metaplastic carcinoma: Post-therapy evaluation of tumor: Metaplastic carcinoma with squamous differentiation (H and E, a: ×40, b: ×100); Squamous pearls (H and E, c: ×200)

Click here to view
Figure 5: Pathologic complete response of breast cancer: Post-therapy evaluation of tumor: Fibrotic stroma (H and E, a: ×40); Granulation tissue with areas of fibrosis, chronic inflammatory cell infiltration and hemorrhage (H and E, b and c: ×40)

Click here to view
Figure 6: Pathologic Complete Response of breast cancer: Post-therapy evaluation of tumor: Intense inflammatory response with areas of fibrosis and absence of tumor cells (H and E, ×40)

Click here to view
Table 1: Carcinoma breast: comparison of effect of therapy

Click here to view
Table 2: Carcinoma breast: correlation of nuclear changes after neoadjuvant therapy

Click here to view
Table 3: Carcinoma breast: correlation of stromal changes/response after neoadjuvant therapy

Click here to view



  Discussion Top


Breast cancer therapy causes morphological alterations in the cancerous as well as the surrounding healthy tissue. However, more commonly changes are described after neoadjuvant chemotherapy (also termed primary systemic therapy or presurgical therapy) in which chemotherapy and hormonal and targeted therapies are administered before the actual surgical excision of the tumor. To have a better insight about the histopathological changes induced by chemotherapy on a breast cancer, the present study analyzed a series of breast cancer cases before and after the therapy. Clinical and histopathological details were collected from a total of 39 cases of breast carcinoma before and posttherapy and the changes induced by the therapy were correlated. Overall, breast cancer is the second most common cancer with India contributing to about 7% of the global burden.[4],[5] In the present study, the most common chief complaint was a palpable swelling in the affected breast while mastalgia (38.5%), discharge from the nipple, and ulcer were the other common complaints noted. The right breast was more commonly involved (66.7%) and upper and outer quadrant was the most common location of the tumor (74.4%) followed by upper and inner quadrant (8%). In 13% of the cases, more than one quadrant was involved. This was in concordance with most of the reported studies wherein upper and outer quadrant was the most common location of the tumor.[6],[7],[8] In the present study, the mean size of the tumor before induction of chemotherapy was 3.75 cm while after chemotherapy, it was found to be 1.75 cm (P < 0.001) indicating a reduction in mean size of the tumor by 50% seen in both small and large tumors in accordance with the study conducted by Fisher et al.,[9] wherein 70%–80% of the patients demonstrated ≥ 50% decrease in the mean size of the tumor. IDC-NOS, being the predominant histological type seen in any breast cancer, was the most common histologic type seen both before (94.87%) and after (76.92%) therapy in the present study, too, while one case each of lobular carcinoma and metaplastic carcinoma was also reported in accordance with most of the previous studies conducted.[6],[10],[11],[12],[13] Therapy and prognosis in breast cancers largely depend on the stage at which the cancer is diagnosed. Breast cancer stage is one of the most important prognostic indicator and significant determinant of the overall survival of the patient. Stage II breast carcinoma was found to be the most predominant (61.5%) stage with Stage IIA accounting for up to 38.5% of the cases. And 23% of the cases were found to be in Stage III in the present study. It was observed that younger women had an aggressive breast cancer with Stage III as the predominant stage noted. These findings were in accordance with the numerous other studies conducted including the one conducted by Orucevic et al.,[14] wherein Stage II breast carcinoma was found to be the most predominant type. Similarly, Stage II was the predominant stage reported in the studies conducted by Faneyte et al.[7] and von Minckwitz et al.[15] with 41% and 52% of the total cases presenting with Stage II tumors, respectively. Narendra and Ray[16] and Gajdos et al.,[17] however, reported majority of the cases belonging to Stage III in their studies in contrast to the above-mentioned studies. Chemotherapy-induced morphological changes were first described by Waller in 1960 when he described cytoplasmic swelling and vacuolation caused by administration of busulfan. Kennedy et al.[10] in 1990, further, described such changes in breast carcinoma patients when combination of tamoxifen and cytotoxic drug therapy was used. Since then, many studies have been published regarding the interaction of chemotherapeutic agents with tumor biology, however, there are very few studies which are detailed enough to include all the parameters such as necrobiotic changes, viability of the tumor cells, and host tissue response to chemotherapeutics agents which could predict response to chemotherapy. In the present study, an elaborative assessment of the cellular and stromal changes was done before and after the therapy. In the stromal changes, generalized increase in collagenization was significantly correlated with pathologic response and grades of tumor regression. The predominant stromal changes seen posttherapy included necrosis (74.4%), fibrosis (64.1%), desmoplasia (59%), and degenerative changes (33.3%) while mucinous changes, hyalinization of walls of blood vessels, neoangiogenesis, calcific deposits, loss of cellular architecture and appearance of chronic inflammatory cell infiltration, and hemosiderin-laden macrophages and giant cells and histiocytes were the other significant stromal changes reported. Sethi et al.[6] reported generalized increase in mucinous and metaplastic changes left after chemotherapy. Honkoop et al.,[12] also, noticed similar mucinous changes left after chemotherapy. This was also in contrast to numerous other studies which did not report any significant histopathological changes postchemotherapy.[12],[18],[19] Gazet et al.[20] also reported that lobular carcinoma was less responsive to chemotherapy due to high stromal content, however, the same could not be substantiated in the present study since only one case each of lobular carcinoma and metaplastic carcinoma was reported in the present study. The fundamental manifestation of the effect of therapy was an obvious decrease in tumor cellularity while the other prominent changes included nuclear enlargement, hyperchromasia, and increased N:C ratio which were found in up to 85% of the cases followed by the presence of prominent nucleoli and karyorrhexis/karyolysis noted in 70%–75% of the cases. Similar changes have also been observed independently in numerous other studies.[6],[14] Such cytological changes are seen because of the cellular damage seen secondary to neoadjuvant chemotherapy as has been hypothesized in other studies and are variable in different tumors after the therapy and the actual change might, further, differ on the chemotherapy regimen used.[9],[21],[22] The true biologic significance of such cytopathic changes in residual breast cancers, though, has received little attention and is poorly understood.[23],[24] Various inflammatory infiltrates might, also, be seen due to host tissue response to the necrobiotic tumor such as appearance of chronic inflammatory cell infiltration and hemosiderin-laden macrophages, intense lymphocytic reactions, presence of plasma cells, and giant cells and histiocytes as described in various studies.[12],[20],[21],[24],[25] Stromal elastosis, too, is seen as a prominent change after therapy.[7],[11],[12],[20],[21] In the present study, response to chemotherapy was classified according to the guidelines of Union for International Cancer Control (UICC) as pathologic Complete Response (pCR) defined as absence of residual viable tumor cells (DCIS: Ductal carcinoma in-situ included), pathologic Partial Response (pPR) as greater than 50% reduction in the number of viable tumor cells, stable disease (SD) as less than 50% reduction in the number of viable tumor cells and/or, no change and progressive disease (PD) as an increase of at least 25% of viable tumor cells. On histopathological examination, pCR was observed in 18% of the cases in the present study, while 15% showed pPR and 66.7% cases had a stable disease with no progression of disease after therapy. pCR was seen in seven of the cases of IDC-NOS type of the tumor, while one case each of lobular, metaplastic, and ductal carcinoma had pPR. Twenty-six cases revealed pathologic no response (pNR) while response in IDC-NOS type of tumor was not significantly different from that observed in invasive lobular carcinoma.

Breast cancer therapy causes morphological alterations in the cancerous as well as the surrounding healthy tissue. The histopathological interpretation in such cases, thus, requires a thorough knowledge of the cytological and stromal changes rendered by the therapy. This ensures the role of the pathologists extremely important in correct diagnosis as well as grading of the tumor with a correct histopathological interpretation for an effective and planned regimen of the therapy increasing prognosis and chances of survival of the affected patients rendering better clinical outcome and an effective patient care.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Babita R, Kumar N, Karwasra RK, Singh M, Malik JS, Kaur A. Reproductive risk factors associated with breast carcinoma in a tertiary care hospital of North India: a case-control study. Indian J Cancer 2014; 51 (3): 251–5.  Back to cited text no. 1
    
2.
Zhang Q, Ma B, Kang M. A retrospective comparative study of clinicopathological features between young and elderly women with breast cancer. Int J Clin Exp Med 2015; 8 (4): 5869–75.  Back to cited text no. 2
    
3.
Leong AS, Zhuang Z. The changing role of pathology in breast cancer diagnosis and therapy. Pathobiology 2011; 78 (2): 99–114.  Back to cited text no. 3
    
4.
Doval DC, Sharma A, Sinha R, Kumar K, Dewan AK, Chaturvedi H, Batra U, Talwar V, Gupta SK, Singh S, Bhole V, Mehta A. Immunohistochemical profile of breast cancer patients at a tertiary care hospital in New Delhi, India. Asian Pac J Cancer Prev 2015; 16 (12): 4959–64.  Back to cited text no. 4
    
5.
Gabriel CA, Domchek SM. Breast cancer in young women. Breast Cancer Res 2010; 12 (5): 212.  Back to cited text no. 5
    
6.
Sethi D, Sen R, Parshad S, Khetarpal S, Garg M, Sen J. Histopathologic changes following neoadjuvant chemotherapy in locally advanced breast cancer. Indian J Cancer 2013; 50 (1): 58–64.  Back to cited text no. 6
    
7.
Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 2003; 88 (3): 406–12.  Back to cited text no. 7
    
8.
Manjer J, Balldin G, Garne JP. Tumour location and axillary lymph node involvement in breast cancer: a series of 3472 cases from Sweden. Eur J Surg Oncol 2004; 30 (6): 610–7.  Back to cited text no. 8
    
9.
Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG. Effect of pre-operative chemotherapy on local-regional disease in women with operable breast cancer: findings from national surgical adjuvant breast and bowel project B-18. J Clin Oncol 1997; 15 (7): 2483–93.  Back to cited text no. 9
    
10.
Bonadonna G, Valagussa P, Zucali R, Salvadori B. Primary chemotherapy in surgically resectable breast cancer. CA Cancer J Clin 1995; 45 (4): 227–43.  Back to cited text no. 10
    
11.
Rasbridge SA, Gillett CE, Seymour AM, Patel K, Richards MA, Rubens RD, Millis RR. The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma. Br J Cancer 1994; 70 (2): 335–41.  Back to cited text no. 11
    
12.
Honkoop AH, Pinedo HM, De Jong JS, Verheul HM, Linn SC, Hoekman K, Wagstaff J, van Diest PJ. Effects of chemotherapy on pathologic and biologic characteristics of locally advanced breast cancer. Am J Clin Pathol 1997; 107 (2): 211–8.  Back to cited text no. 12
    
13.
Burcombe RJ, Makris A, Richman PI, Daley FM, Noble S, Pittam M, Wright D, Allen SA, Dove J, Wilson GD. Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer. Br J Cancer 2005; 92 (1): 147–55.  Back to cited text no. 13
    
14.
Orucevic A, Chen J, McLoughlin JM, Heidel RE, Panella T, Bell J. Is the TNM staging system for breast cancer still relevant in the era of biomarkers and mmerging personalized medicine for breast cancer: an institution's 10-year experience. Breast J 2015; 21 (2): 147–54.  Back to cited text no. 14
    
15.
von Minckwitz G, Costa SD, Eiermann W, Blohmer JU, Tulusan AH, Jackisch C, Kaufmann M. Maximized reduction of primary breast tumor size using pre-operative chemotherapy with doxorubicin and docetaxel. J Clin Oncol 1999; 17 (7): 1999–2005.  Back to cited text no. 15
    
16.
Narendra H, Ray S. Breast conserving surgery for breast cancer: single institutional experience from Southern India. Indian J Cancer 2011; 48 (4): 415–22.  Back to cited text no. 16
    
17.
Gajdos C, Tartter PI, Estabrook A, Gistrak MA, Jaffer S, Bleiweiss IJ. Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer. J Surg Oncol 2002; 80 (1): 4–11.  Back to cited text no. 17
    
18.
van der Wall E, Rutgers EJ, Holtkamp MJ, Baars JW, Schornagel JH, Peterse JL, Beijnen JH, Rodenhuis S. Efficacy of up-front 5-fluorouracil-epidoxorubicin-cyclophosphamide (FEC) chemotherapy with an increased dose of epidoxorubicin in high-risk breast cancer patients. Br J Cancer 1996; 73 (9): 1080–5.  Back to cited text no. 18
    
19.
Demaria S, Volm MD, Shapiro RL, Yee HT, Oratz R, Formenti SC, Muggia F, Symmans WF. Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clin Cancer Res 2001; 7 (10): 3025–30.  Back to cited text no. 19
    
20.
Gazet JC, Coombes RC, Ford HT, Griffin M, Corbishley C, Makinde V. Assessment of the effect of pretreatment with neoadjuvant therapy on primary breast cancer. Br J Cancer 1996; 73 (6): 758–62.  Back to cited text no. 20
    
21.
Morrow M, Braveman A, Thelmo W, Sohn CK, Sand J, Mora M, Forlenza T, Marti J. Multimodal therapy for locally advanced breast cancer. Arch Surg 1986; 121 (11): 1291–6.  Back to cited text no. 21
    
22.
Niu S, Wen G, Ren Y, Li Y, Feng L, Wang C, Huang X, Wen B, Zhang Y. Predictive value of primary tumor site for loco-regional recurrence in early breast cancer patients with one to three positive axillary lymphadenophy. J Cancer 2017; 8 (12): 2394–400.  Back to cited text no. 22
    
23.
Rajan R, Esteva FJ, Symmans WF. Pathologic changes in breast cancer following neoadjuvant chemotherapy: implications for the assessment of response. Clin Breast Cancer 2004; 5 (3): 235–8.  Back to cited text no. 23
    
24.
Moreno A, Escobedo A, Benito E, Serra JM, Gumà A, Riu F. Pathologic changes related to CMF primary chemotherapy in breast cancer: pathological evaluation of response predicts clinical outcome. Breast Cancer Res Treat 2002; 75 (2): 119–25.  Back to cited text no. 24
    
25.
Moon YW, Rha SY, Jeung HC, Yang WI, Suh CO, Chung HC. Neoadjuvant chemotherapy with infusional 5-fluorouracil, adriamycin and cyclophosphamide (iFAC) in locally advanced breast cancer: an early response predicts good prognosis. Ann Oncol 2005; 16 (11): 1778–85.  Back to cited text no. 25
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed2324    
    Printed91    
    Emailed0    
    PDF Downloaded361    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]