Published online: 2019-03-04

THIEME
Original Article 61

Histopathological Changes in Breast Cancers

Following Neoadjuvant Chemotherapy: Implications
for Assessment of Therapy-Induced Cytological and
Stromal Changes for Better Clinical Outcome and
Effective Patient care
Shazima Sheereen1 Flora D. Lobo1 Barun Kumar2 Manoj Kumar S.3 Santosh Reddy G.4
Waseemoddin Patel5 Abhishek Singh Nayyar6

1Department of Pathology, Kasturba Medical College, Manipal Academy Address for correspondence Shazima Sheereen, Department of Pathology,
of Higher Education, Mangalore, Karnataka, India Kasturba Medical College, Manipal Academy of Higher Education,
2Department of Oral and Maxillofacial Surgery, Bharati Vidyapeeth Mangalore, Karnataka, India (e-mail: dr.shazimasheereen@gmail.com).
(Deemed to be University) Dental College and Hospital, Sangli,
Maharashtra, India
3Department of Oral Radiology, College of Dentistry, University of Ha’il,
Ha’il, Kingdom of Saudi Arabia
4Department of Oral and Maxillofacial Surgery, Malla Reddy Dental
College for Women, Hyderabad, Telangana, India
5Department of Pediatrics and Neonatology, McMaster University,
Hamilton, Ontario, Canada
6 Department of Oral Medicine and Radiology, Saraswati-
Dhanwantari Dental College and Hospital and Postgraduate
Research Institute, Parbhani, Maharashtra, India

Asian J Oncol 2018;4:61–68

Abstract The histopathological interpretation of a tumor still remains the gold standard
for diagnosis and deciding the type of therapy. Furthermore, in the context of
chemo-radio-therapies often leading to prominent cytological and s­ tromal changes
in the tumor, histopathological interpretation during treatment, thus, becomes all
the more important in correctly diagnosing and grading the tumor for an effective
and planned regimen of the therapy increasing prognosis and chances of survival of
the affected patients. The aim of the present study was to evaluate such cytological
and stromal changes rendered by the therapy during treatment in breast cancer
cases. The present study was conducted over a period of 4 years from January 2014
Keywords to June 2017 at Kasturba Medical College, Mangalore, Karnataka, India wherein the
►►therapy-induced clinical and histopathological details were collected for a total of 39 breast carcinoma
histopathological cases during and post-therapy. Statistical analysis was done using IBM SPSS statistics
changes 17 (­Chicago, USA). Various morphological features were analyzed for their frequency
►►breast cancers and were compared with the final diagnosis using Chi-square value (χ2), paired
►►neoadjuvant t-test and Fischer’s test. p-value < 0.05 was considered to be statistically significant.
chemotherapy The results of the present study revealed that 32 of the 39 breast carcinoma cases
►►breast cancer diagnosis changed their grades during the course of therapy (p-value < 0.05). The fundamental
and treatment manifestation of the effect of therapy was an obvious decrease in tumor cellularity.

DOI https://doi.org/ ©2018 Spring Hope Cancer

10.1055/s-0038-1676909 Foundation & Young Oncologist
ISSN 2454-6798. Group of Asia
62 Therapy-Induced Histopathological Changes in Breast Cancers Sheereen et al.

Intracellular changes commonly noted after chemotherapy included n ­ uclear enlarge-

ment, hyperchromasia and an increased N:C ratio which were found in upto 85% of
the cases followed by presence of prominent nucleoli and ­karyorrhexis/karyolysis. The
predominant stromal changes seen post-therapy included necrosis (74.4%), fibrosis
(64.1%), desmoplasia (59%) and degenerative changes (33.3%). 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.

Introduction r­ endered by the therapy in breast cancer cases. This ensures the
role of pathologists in the correct diagnosis as well as grading of
Breast cancer is the most common cancer diagnosed in women
the tumor with a correct histopathologic interpretation for an
and is the second leading cause of death in women globally.1
effective and planned regimen of the therapy increasing prog-
Even though most cases occur over the age of 50 years, it is not
nosis and chances of survival of the affected patients rendering
uncommon in younger women.1,2 Breast cancer is not a single
better clinical outcome and an effective patient care.
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 Materials and Methods
and fine-needle aspiration cytology (FNAC) often help in the This study was a combined retrospective and prospective
diagnosis of breast cancers. However, histopathologic exam- study conducted over a period of 4 years from January
ination remains the better predictor for an accurate diagnosis 2014 to June 2017 at Kasturba Medical College, Mangalore,
of breast cancers. In addition, immunohistochemical markers Karnataka, India. Clinical and histopathologic details were
aid in classification and are often used to guide the therapy of collected from a total of 39 cases of breast carcinoma before
the disease process. Therapy and prognosis depend on the var- and post-therapy, and the changes induced by the therapy
ious clinical and histopathologic factors, including tumor size, were correlated. All the patients who had been diagnosed
type of tumor, hormonal receptor status, the type of therapy with stages II and III (T1–T4, N0–2, M0) carcinoma breast
provided, and, most significantly, at what stage the cancer is were included in the study while patients already treated
diagnosed. Because of extensive advances made in the field of with chemo- or hormonal therapy and patients who only
oncology, various modes of therapy of breast cancers are avail- underwent surgery without chemo- or hormonal therapy
able at present including surgery, radiotherapy, chemotherapy, and wherein biopsy samples were found to be inadequate
and, more specifically, targeted hormonal and tumor receptors were excluded. The required clinical data of the patients,
targeted therapy. Surgery that may include mastectomy or, their lymph node status, and investigation reports
breast-conserving surgery (lumpectomy), still remains the (mammography, FNAC, biopsy, ER/PR status, Her2/neu
prime modality of therapy for most of the operable breast status) were collected before the start of the planned therapy.
­cancers. Hormonal therapy can be a significant addition along The initial biopsies were subjected to routine formalin
with surgery or, chemotherapy, especially, in patients who fixation and paraffin processing with microscopic analysis
are estrogen receptor (ER) and/or, progesterone receptor (PR) on hematoxylin and eosin–stained sections supplemented
positive. Hormonal receptor status can, thus, significantly by special stains including immunohistochemistry to
alter the modality of therapy provided and may have better decide the histologic types and grades of the tumor
outcomes. In advanced disease, prior to surgery, radiation ther- and hormonal status. Subsequently, when the patients
apy is used to reduce the tumor size. In early breast cancers, to received two to six cycles of chemotherapy or, hormonal
facilitate breast conservation, chemotherapy is more commonly therapy, histopathologic (gross and microscopic) and
used both as a neoadjuvant chemotherapy and/or postopera- immunohistochemical examination was performed and all
tive chemotherapy.4 In the modern era, increased number of the details pertaining to microscopic and clinical findings
­neoadjuvant therapy-induced surgical resection specimens of along with immunohistochemical findings were recorded
tumors are being received in histopathologic evaluation labora- and the changes induced by therapy were correlated.
tories. The pathologist evaluates the residual tumor both in the
breast and lymph nodes. Assessment of the therapy-induced Statistical Analysis
morphologic changes seen at the cytologic and stromal levels, Statistical analysis was done using IBM SPSS statistics
thus, requires a thorough knowledge of the possible cytologic 17 (Chicago, Illinois, USA). The data were analyzed
and stromal changes rendered by the therapy. The aim of this by proportions, tables, and graphs whereas various
study was to evaluate such cytologic and stromal changes morphologic features were analyzed for their frequency and

Asian Journal of Oncology Vol. 4 No. 2/2018

 Therapy-Induced Histopathological Changes in Breast Cancers Sheereen et al. 63

were compared with the final diagnosis using chi-square regimen received was CAF (cyclophosphamide, doxorubicin,
value (χ2), paired t-test, and Fischer’s test. p < 0.05 was 5-fluorouracil) followed by CEF (cyclophosphamide,
considered to be statistically significant whereas p < 0.001 epirubicin, 5-fluorouracil) regimen (6 cases, 15.38%). The
was considered as highly significant. mean size of the tumor before induction of chemotherapy
was found to be 3.75 cm whereas after chemotherapy it
was 1.75 cm (p < 0.001). The tumor size decreased con-
Results
sistently after neoadjuvant chemotherapy. Stage II breast
This study consisted of 39 breast carcinoma cases. The carcinoma was found to be the most predominant (61.5%)
­median age of patients was found to be 55 years. The most stage with stage IIA accounting for up to 38.5% of the cases,
common chief complaint was a palpable swelling in the and 23% of the cases were found to be in stage III. It was
affected breast whereas mastalgia (38.5%), discharge from observed that younger women had an aggressive breast
nipple, and ulcer were the other common complaints. The cancer with stage III as the predominant stage noted. IDC-
right breast was more commonly involved (66.7%), and NOC (infiltrating ductal carcinoma–not otherwise specified)
upper and outer quadrant was the most common location (►Figs. 1–15) was the most common histologic type both
of the tumor (74.4%) followed by upper and inner ­quadrant before (94.87%) and after (76.92%) therapy. One case of
(8%). In 13% of the cases, more than one quadrant was lobular carcinoma and one case of metaplastic carcinoma
involved. Most cases (69%) in this study received four to six (►Figs. 16–18) were also found. Thirty-two of the 39 tumors
cycles of neoadjuvant chemotherapy whereas 31% of cases changed grade to either a higher or lower grade (p < 0.05). On
received more than six cycles of chemotherapy. AC regimen histopathologic examination, pathologic complete response
(­
doxorubicin, cyclophosphamide followed by paclitaxel) (pCR) (►Figs. 19–21) was observed in 18% of the cases
was the most common (26 cases, 64.1%) chemotherapy whereas 15% showed pathologic partial response (pPR) and
regimen received. The second most common (8 cases, 20.5%) 66.7% cases had a stable disease (SD) with no progression

Fig. 2 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified:

Fig. 1 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified: Post-therapy evaluation of tumor: Lymph nodal tissue showing residual
Post-therapy evaluation of tumor: Tumor cells (H&E, 40x). tumor cells with areas of fibrosis and hyalinization (H&E, 100x).

Fig. 3 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified: Fig. 4 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified:
Post-therapy evaluation of tumor: Residual tumor cells showing areas of Post-therapy evaluation of tumor: Residual tumor cells showing
fibrosis and calcification (H&E, 200x). hemosiderin laden macrophages along with areas of fibrosis (H&E, 40x).

Fig. 5 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified: Fig. 6 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified:
Post-therapy evaluation of tumor: Residual tumor cells showing hemosiderin Post-therapy evaluation of tumor: Residual tumor cells showing hemosiderin
laden macrophages along with areas of fibrosis (H&E, 100x). laden macrophages along with areas of fibrosis (H&E, 200x).

Asian Journal of Oncology Vol. 4 No. 2/2018

64 Therapy-Induced Histopathological Changes in Breast Cancers Sheereen et al.

Fig. 7 IDC-NOC: Infiltrating ductal carcinoma-not otherwise Fig. 8 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified:
specified: Post-therapy evaluation of tumor: Perinodal fat infiltration Post-therapy evaluation of tumor: Residual tumor cells in lymph nodal
of tumor cells (H&E, 100x). tissue (H&E, 200x).

Fig. 9 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified: Fig. 10 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified:
Post-therapy evaluation of tumor: Residual tumor cells in lymph nodal Post-therapy evaluation of tumor: Residual tumor cells showing areas of
tissue (H&E, 400x). fibrosis and calcification (H&E, 100x).

Fig. 11 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified: Fig. 12 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified:
Post-therapy evaluation of tumor: Residual tumor cells showing areas of Post-therapy evaluation of tumor: Tumor in skeletal muscle (H&E, 40x).
fibrosis and calcification (H&E, 200x).

Fig. 13 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified: Fig. 14 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified:
Post-therapy evaluation of tumor: Tumor in skeletal muscle (H&E, 200x). Post-therapy evaluation of tumor: Lymphovascular invasion (H&E, 100x).

Fig. 15 IDC-NOC: Infiltrating ductal carcinoma-not otherwise specified: Fig. 16 Metaplastic carcinoma: Post-therapy evaluation of tumor:
Post-therapy evaluation of tumor: Neural invasion (H&E, 200x). Metaplastic carcinoma with squamous differentiation (H&E, 40x).

Asian Journal of Oncology Vol. 4 No. 2/2018

 Therapy-Induced Histopathological Changes in Breast Cancers Sheereen et al. 65

of disease (►Table 1). The fundamental manifestation of stromal changes included mucinous changes, hyalinization
the effect of therapy was an obvious decrease in tumor of walls of blood vessels, (►Fig. 2) neo-angiogenesis, calcific
cellularity. Intracellular changes commonly noted after deposits (►Figs. 3, 10, 11), loss of cellular architecture,
chemotherapy-included nuclear enlargement, hyperchro- and appearance of chronic inflammatory cell infiltration
masia, and increased nuclear-to-cytoplasmic (N:C) ratio (►Figs. 20–21) and hemosiderin-laden macrophages
that were found in up to 85% of the cases, followed by (►Figs. 4–6), giant cells, and histiocytes (►Table 3).
presence of prominent nucleoli and karyorrhexis/karyolysis
noted in 70 to 75% of the cases (►Table 2). The predominant
Discussion
stromal changes seen post-therapy were necrosis (74.4%),
fibrosis (64.1%) (►Figs. 2–6, 10, 11, 19–21), desmoplasia Breast cancer therapy causes morphologic alterations in the
(59%), and degenerative changes (33.3%). Other significant cancerous as well as the surrounding healthy tissue. However,

Fig. 17 Metaplastic carcinoma: Post-therapy evaluation of tumor: Fig. 18 Metaplastic carcinoma: Post-therapy evaluation of tumor:
Metaplastic carcinoma with squamous differentiation (H&E, 100x). Squamous pearls (H&E, 200x).

Fig. 19 pCR: pathologic complete response of breast cancer: Post-therapy Fig. 20 (A,B) pCR: pathologic complete response of breast cancer:
evaluation of tumor: Fibrotic stroma (H&E, 40x). Post-therapy evaluation of tumor: Granulation tissue with areas of
fibrosis, chronic inflammatory cell infiltration and hemorrhage.

Fig. 21 (A–C) Inflammatory response with areas of fibrosis and absence of tumor cells.

Table 1 Carcinoma breast: comparison of effect of therapy

Effect of Obtained in study Obtained in study Obtained in Obtained in Obtained in this
therapy conducted by van conducted by study conducted study conducted study (n = 39), n (%)
der Wall et al18 Burcombe et al13 by Moon et al25 by Sethi et al6
(n = 62), n (%) (n = 99), n (%) (n = 82), n (%) (n = 40), n (%)
pCR 13/62 (21) 8/99 (8) 21 (25) 4/40 (10) 7/39 (17.9)
pPR 42/62 (68) 30/99 (30) 49 (59) 12/40 (30) 6/39 (15.4)
pNR 7/62 (11) 61/99 (62) 12 (15) 24/40 (60) 26/39 (66.7)
Abbreviations: pCR, pathologic complete response; pNR, pathologic no response; pPR, pathologic partial response.

Asian Journal of Oncology Vol. 4 No. 2/2018

66 Therapy-Induced Histopathological Changes in Breast Cancers Sheereen et al.

the median age of breast cancer patients was found to be

Table 2 Carcinoma breast: correlation of nuclear changes
46 and 45 years, respectively. In this study, the most common
after neoadjuvant therapy
chief complaint was a palpable swelling in the affected breast
Nuclear response Number of cases (%)
whereas mastalgia (38.5%), discharge from nipple, and ulcer
Nuclear enlargement 35 (89.7) were the other common complaints noted. The right breast
Hyperchromasia 34 (87.2) was more commonly involved (66.7%), and upper and outer
Increased nuclear-to-cytoplasmic 33 (84.6) quadrant was the most common location of the tumor (74.4%)
ratio followed by upper and inner quadrant (8%). In 13% of the
Presence of prominent nucleoli 30 (76.9) ­cases, more than one q ­ uadrant was involved. This was in con-
cordance with most of the reported studies wherein upper
Karyorrhexis/karyolysis 28 (71.8)
and outer quadrant was the most common location of the
Pyknosis 23 (59)
tumor.6,8 Interestingly, in this study, the mean size of the
Pleomorphic nuclei 24 (61.5) tumor before induction of c­hemotherapy was found to be
3.75 cm whereas after chemotherapy it was 1.75 cm
Table 3 Carcinoma breast: correlation of stromal changes/ (p < 0.001), indicating a reduction in mean size of the tumor
response after neoadjuvant therapy by 50% seen in both small and large tumors in contrast with
the study conducted by Fisher et al9 wherein 70 to 80% of the
Stromal change/response Number of cases (%)
patients demonstrated > 50% decrease in the mean size of the
Elastosis/collagenization 14 (35.9) tumor. As it is a known fact that IDC-NOC is the predominant
Fibrosis 25 (64.1) histologic type seen in any breast cancer, IDC-NOC was the
Necrosis 29 (74.4) most common histologic type seen both before (94.87%) and
Desmoplasia 23 (59) after (76.92%) therapy in this study whereas one case each of
lobular carcinoma and metaplastic carcinoma was also
Hyalinization of the walls of blood 2 (5.1)
vessels reported in conjunction with most of the previous stud-
ies.6,10-13 Therapy and prognosis in breast c­ancers largely
Calcification 9 (23.1)
depend on the stage at which the cancer is ­diagnosed. Breast
Mucinous change 3 (7.7) cancer stage is one of the most important prognostic indica-
Foamy histiocytes 8 (20.5) tors and significant determinant of the patient’s overall
Cancerization of lobules 10 (25.6) ­survival. Stage II breast carcinoma was found to be the most
Angiogenesis 9 (23.1) 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
Giant cells 14 (35.9)
stage III in this study. It was observed that younger women
Atrophy of adjacent breast 7 (17.9) had an aggressive breast cancer with stage III as the predom-
parenchyma
inant stage noted. These findings were in accordance with the
Degenerative changes 13 (33.3) numerous other studies conducted including the one con-
Hemosiderin-laden macrophages 7 (17.9) ducted by Orucevic et al14 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
more commonly changes are described after neoadjuvant by Faneyte et al7 and von Minckwitz et al15 with 41% and 52%
c­ hemotherapy (also, termed primary systemic therapy or pre- of the total cases presenting with stage II tumors, ­respectively.
surgical therapy) in which chemotherapy and hormonal and Narendra and Ray16 and Gajdos et al,17 however, ­reported most
­targeted therapies are administered before the actual surgical cases belonging to stage III in their studies in contrast to the
excision of the tumor. To have a better insight about the histo- aforementioned studies. Chemotherapy-­induced ­morphologic
pathologic changes induced by chemotherapy on a breast changes were first described by Waller in 1960 when he
cancer, this study analyzed a series of breast cancer cases described cytoplasmic swelling and v ­ acuolation caused by
before and after the therapy. Clinical and histopathologic administration of busulfan. Kennedy et al in 1990 further
details were collected from a total of 39 cases of breast carci- described such changes in patients with breast carcinoma
noma before and post-therapy, and the changes induced by when combination of tamoxifen and c­ ytotoxic drug therapy
the therapy were correlated. Overall, breast cancer is the was used. Since then, many studies have been published
second most common cancer with India contributing to
­ regarding the ­interaction of chemotherapeutic agents with
approximately 7% of the global burden.4,5 Because age is one of tumor biology; however, there are very few studies that are
the most important risk factor for breast cancers, the inci- detailed enough to include all the parameters such as necro-
dence of breast ­cancers is seen to increase with age with most biotic changes, viability of the tumor cells and host tissue
women getting diagnosed with breast cancers after the age of response to chemotherapeutics agents, etc., which could pre-
40 years in their lives. In this study, the median age of breast dict response to chemotherapy. In this study, an elaborative
carcinoma patients was found to be 55 years in contrast to the assessment of the cellular and stromal changes was done
­studies conducted by Sethi et al6 and Faneyte et al7 wherein before and after the therapy. In the stromal changes,

Asian Journal of Oncology Vol. 4 No. 2/2018

 Therapy-Induced Histopathological Changes in Breast Cancers Sheereen et al. 67

generalized increase in collagenization was significantly cor- Conclusion

related with pathologic response and grades of tumor regres-
sion. The predominant stromal changes seen post-therapy Breast cancer therapy causes morphologic alterations in
included necrosis (74.4%), fibrosis (64.1%), desmoplasia (59%), the cancerous as well as the surrounding healthy tissue. The
and degenerative changes (33.3%) whereas mucinous chang- histopathologic interpretation in such cases, thus, requires
es, hyalinization of walls of blood vessels, neo-angiogenesis, a thorough knowledge of the cytologic and stromal changes
­calcific deposits, loss of cellular architecture, and appearance rendered by the therapy. This ensures the role of the pathologists
of chronic inflammatory cell infiltration and hemosiderin-­ extremely important in correct diagnosis as well as grading of
laden macrophages, giant cells, and histiocytes were the other the tumor with a correct histopathologic interpretation for an
significant stromal changes reported. Sethi et al6 reported effective and planned regimen of the therapy increasing prog-
generalized increase in mucinous and metaplastic changes nosis and chances of survival of the affected patients rendering
left after ­chemotherapy. Honkoop et al12 also noticed similar better clinical outcome and an effective patient care.
mucinous changes left after chemotherapy. This was also in Funding
contrast to numerous other studies that did not report any None.
significant histopathologic changes post-chemotherapy.12,18,19
Gazet et al20 also reported that lobular carcinoma was less Conflict of Interest
responsive to chemotherapy due to high stromal content; None declared.
however, the same could not be s­ ubstantiated in this study Acknowledgments
because only one case each of lobular carcinoma and The authors would like to thank all the patients who
metaplastic carcinoma was reported in this study. The contributed in the study without whom this study would
fundamental manifestation of the effect of therapy was an not have been feasible.
obvious decrease in tumor cellularity whereas the other
prominent changes included nuclear enlargement,
References
hyperchromasia, and increased N:C ratio that were found in
up to 85% of the cases followed by presence of prominent 1 Babita R, Kumar N, Karwasra RK, Singh M, Malik JS, Kaur A.
Reproductive risk factors associated with breast carcinoma in
nucleoli and karyorrhexis/karyolysis noted in 70 to 75% of the
a tertiary care hospital of north India: a case-control study.
cases. Similar changes have also been observed independently Indian J Cancer 2014;51(3):251–255
in numerous other studies.6,14 Such cytologic changes are seen 2 Zhang Q, Ma B, Kang M. A retrospective comparative study of
because of the cellular damage seen secondary to neoadju- clinicopathological features between young and elderly women
vant chemotherapy as has been hypothesized in other studies with breast cancer. Int J Clin Exp Med 2015;8(4):5869–5875
3 Leong AS, Zhuang Z. The changing role of pathology in
and are variable in different tumors after the therapy, and the
breast cancer diagnosis and treatment. Pathobiology
actual change might further differ on the chemotherapy
2011;78(2):99–114
­regimen used.9,21,22 The true biologic significance of such cyto- 4 Doval DC, Sharma A, Sinha R, et al. Immunohistochemical
pathic changes in residual breast cancers, however, has profile of breast cancer patients at a tertiary care
received little attention and is poorly understood.23,24 Various hospital in New Delhi, India. Asian Pac J Cancer Prev
inflammatory infiltrates might also be seen due to host tissue 2015;16(12):4959–4964
5 Gabriel CA, Domchek SM. Breast cancer in young women.
response to the necrobiotic tumor such as appearance of
Breast Cancer Res 2010;12(5):212
chronic inflammatory cell infiltration and hemosiderin-laden 6 Sethi D, Sen R, Parshad S, Khetarpal S, Garg M, Sen J.
macrophages, intense lymphocytic reactions, presence of Histopathologic changes following neoadjuvant chemotherapy
plasma cells, and giant cells, and histiocytes as described in in locally advanced breast cancer. Indian J Cancer 2013;
various studies.12,20,21,24,25 Stromal elastosis too is seen as a 50(1):58–64
prominent change after therapy.7,11,12,20,21 In this study, 7 Faneyte IF, Schrama JG, Peterse JL, Remijnse PL,
Rodenhuis S, van de Vijver MJ. Breast cancer response to
response to chemotherapy was classified according to the
neoadjuvant chemotherapy: predictive markers and relation
International Union against Cancer (UICC) as pCR defined as with outcome. Br J Cancer 2003;88(3):406–412
absence of residual viable tumor cells (DCIS included), pPR as 8 Manjer J, Balldin G, Garne JP. Tumour location and axillary
greater than 50% reduction in the number of viable tumor lymph node involvement in breast cancer: a series of 3472
cells, SD as less than 50% reduction in the number of viable cases from Sweden. Eur J Surg Oncol 2004;30(6):610–617
9 Fisher B, Brown A, Mamounas E, et al. Effect of preoperative
tumor cells, or no change and progressive disease (PD) as an
chemotherapy on local-regional disease in women with
increase of at least 25% of viable tumor cells. On histopathologic
operable breast cancer: findings from National Surgical
examination, pCR was observed in 18% of the cases in this Adjuvant Breast and Bowel Project B-18. J Clin Oncol
study whereas 15% showed pPR and 66.7% cases had an SD 1997;15(7):2483–2493
with no progression of disease after therapy. pCR was seen in 10 Bonadonna G, Valagussa P, Zucali R, Salvadori B. Primary
seven of the cases of IDC-NOC type of the tumor whereas one chemotherapy in surgically resectable breast cancer. CA Cancer
J Clin 1995;45(4):227–243
case each of lobular, metaplastic, and ductal carcinoma had
11 Rasbridge SA, Gillett CE, Seymour AM, et al. The effects
pPR. ­Twenty-six cases revealed pNR whereas response in IDC- of chemotherapy on morphology, cellular proliferation,
NOC type of tumor was not significantly different from that apoptosis and oncoprotein expression in primary breast car-
observed in invasive lobular carcinoma. cinoma. Br J Cancer 1994;70(2):335–341

Asian Journal of Oncology Vol. 4 No. 2/2018

68 Therapy-Induced Histopathological Changes in Breast Cancers Sheereen et al.

12 Honkoop AH, Pinedo HM, De Jong JS, et al. Effects of 19 Demaria S, Volm MD, Shapiro RL, et al. Development of
chemotherapy on pathologic and biologic characteristics tumor-infiltrating lymphocytes in breast cancer after
of locally advanced breast cancer. Am J Clin Pathol neoadjuvant paclitaxel chemotherapy. Clin Cancer Res
1997;107(2):211–218 2001;7(10):3025–3030
13 Burcombe RJ, Makris A, Richman PI, et al. Evaluation of ER, 20 Gazet JC, Coombes RC, Ford HT, et al. Assessment of the effect
PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant of pretreatment with neoadjuvant therapy on primary breast
anthracycline chemotherapy for operable breast cancer. cancer. Br J Cancer 1996;73(6):758–762
Br J Cancer 2005;92(1):147–155 21 Morrow M, Braverman A, Thelmo W, et al. Multimodal
14 Orucevic A, Chen J, McLoughlin JM, Heidel RE, Panella T, Bell therapy for locally advanced breast cancer. Arch Surg
J. Is the TNM staging system for breast cancer still relevant in 1986;121(11):1291–1296
the era of biomarkers and emerging personalized medicine 22 Niu S, Wen G, Ren Y, et al. Predictive value of primary tumor
for breast cancer—an institution’s 10-year experience. site for loco-regional recurrence in early breast cancer patients
Breast J 2015;21(2):147–154 with one to three positive axillary lymphadenopathy. J Cancer
15 von Minckwitz G, Costa SD, Eiermann W, et al. Maximized 2017;8(12):2394–2400
reduction of primary breast tumor size using preoperative 23 Rajan R, Esteva FJ, Symmans WF. Pathologic changes in breast
chemotherapy with doxorubicin and docetaxel. J Clin Oncol cancer following neoadjuvant chemotherapy: implications
1999;17(7):1999–2005 for the assessment of response. Clin Breast Cancer
16 Narendra H, Ray S. Breast conserving surgery for breast cancer: 2004;5(3):235–238
single institutional experience from Southern India. Indian J 24 Moreno A, Escobedo A, Benito E, Serra JM, Gumà A, Riu F.
Cancer 2011;48(4):415–422 Pathologic changes related to CMF primary chemotherapy in
17 Gajdos C, Tartter PI, Estabrook A, Gistrak MA, Jaffer S, breast cancer. Pathological evaluation of response predicts
Bleiweiss IJ. Relationship of clinical and pathologic response to clinical outcome. Breast Cancer Res Treat 2002;75(2):119–125
neoadjuvant chemotherapy and outcome of locally advanced 25 Moon YW, Rha SY, Jeung HC, Yang WI, Suh CO, Chung HC.
breast cancer. J Surg Oncol 2002;80(1):4–11 Neoadjuvant chemotherapy with infusional 5-fluorouracil,
18 van der Wall E, Rutgers EJ, Holtkamp MJ, et al. Efficacy of Adriamycin and cyclophosphamide (iFAC) in locally advanced
up-front 5-fluorouracil-epidoxorubicin-cyclophosphamide breast cancer: an early response predicts good prognosis. Ann
(FEC) chemotherapy with an increased dose of epidoxo- Oncol 2005;16(11):1778–1785
rubicin in high-risk breast cancer patients. Br J Cancer
1996;73(9):1080–1085

Asian Journal of Oncology Vol. 4 No. 2/2018