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Clinical Journal of Surgery  •  Vol 1  •  Issue 1  •  2018 20
INTRODUCTION
N
eoadjuvant chemotherapy (NAC) offers a series of
advantages in patients with breast cancer, making
it an important treatment option to be taken into
account by multidisciplinary teams. Although a review of
the current scientific evidence suggests its efficacy, the use
of NAC remains highly variable.[1]
Herein, we analyze our
clinical experience with the use of NAC in a mammary ductal
carcinoma, with the aim of helping multidisciplinary teams to
identify patient suitability for neoadjuvant support.
CASE REPORT
We would like to contribute our experience regarding the
findings in a 45-year-old female patient with a cochlear implant
and no other relevant conditions who had a breast nodule
identified during routine examination. The study showed a
12 mm tumor with evident axillary lymphadenopathy, which
was found to be an infiltrating ductal carcinoma 100% estrogen
receptor positive, 5% progesterone receptor positive, human
epidermal growth factor receptor type 2 (HER2) negative, with
Ki67 at 30%, and axillary metastasis.
Following radiographic marking for both lesions, NAC
was initiated (Adriamycin, cyclophosphamide, and
docetaxel), which resulted in complete radiographic response
(mammography and ultrasonography, since magnetic resonance
imaging was unfeasible). During surgery, the tumor area was
excised under harpoon guidance, and then, the clip-marked
axillary lymphadenectomy was also removed and analyzed.The
pathology study confirmed a complete pathological response
(CPR) in both the breast and marked lymph node, but not in
the rest of the axilla, where another lymph node developed
macrometastasis and tumor-related capsular rupture [Figure 1].
DISCUSSION
Progression during neoadjuvant therapy is a truly strange
clinical finding even for a very experienced surgeon, with
a rate of 3% in a meta-analysis of 1928 cases published by
Caudle et al., in 2011.[2]
In this case, response to NAC is seemingly inconsistent in
the breast and the axilla for the same tumor. NAC facilitates
surgery,assessesresponsetotherapy,andprovidesaprognostic
factor more effectively than systemic therapy after surgery.[3-6]
It is consequently very important for the specialized team
CASE REPORT
Confused Response to Neoadjuvant Therapy in
Breast Cancer
Antonio José Fernández López, Francisco Miguel González Valverde
Department of Surgery, Pediatrics, Obstetrics and Gynecology, University of Murcia, Reina Sofía General
University Hospital, Murcia, Spain
ABSTRACT
Neoadjuvant chemotherapy (NAC) brings a series of benefits for patients with mammary neoplasms. While literature shows its
effectiveness, the utilization of NAC remains highly variable. Herein, we analyze our clinical experience with the use of NAC
in an infiltrating ductal carcinoma with evident axillary lymphadenopathy. In this rare case, response to NAC is seemingly
inconsistent in the breast and the axilla for the same tumor.
Key words: Axillary macrometastasis, breast cancer, chemotherapy, neoadjuvant treatment, patient management
Address for correspondence:
Francisco Miguel González Valverde, C/Victorio 3, 2°C. 30003, Murcia, Spain. Phone: +34653571036.
E-mail: 
https://doi.org/10.33309/2639-9164.010107 www.asclepiusopen.com
© 2018 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
Fernandez López and González Valverde: Neoadjuvant therapy for breast cancer
21 Clinical Journal of Surgery  •  Vol 1  •  Issue 1  •  2018
to take into account the advantages and possible risks when
selecting subjects who may gain from NAC.
While extensive agreement exits regard the group of patients
most likely to benefit from NAC, its use in clinical practice
varies widely. In any case, a number of factors must be
allowed for when selecting patients for NAC:
•	 Patients presenting with inoperable locally advanced
breast neoplasm
•	 Young age
•	 High tumor volume-to-breast ratio
•	 All early-stage breast cancer patient, as they could
probably benefit from NAC before surgery
•	 Axillary lymph node-positive disease
•	 Biological features of primitive cancer (positive HER2,
high grade, hormone receptor negative, and triple-
negative breast cancer).
The efficacy of NAC is assessed by evaluating the clinical
and radiological response during and after therapy and the
pathological response after surgery. With nuances, CPR is
defined as the complete clearance of the infiltrating component
bothinthebreastandtheaxilla;hence,itrepresentsasignificant
predictive factor for survival and disease-free interval.[7-9]
CPR primarily depends on molecular phenotype. Good
CPR rates are obtained in 31–60% of HER2 subtypes,
34–40% of triple-negative tumors, and 10% of luminal
A and B types.[3,4,7]
Furthermore, in luminal B tumors, CPR
also depends on the Ki67 proliferation index and histologic
grade; our patient had a high Ki67 at 30%.
Both the sentinel node biopsy and clip-marked node biopsy
offer a relevant number of false-negative results for axillary
node metastasis after NAC.[1,10]
Therefore, in the absence of comparative studies with
adequate follow-up to provide true guidelines, potential
residual disease in the axilla,[4,5]
the effect of radiotherapy,
and the impact of it all on overall survival make up the big
enigma regarding breast cancer today. On the other hand, the
fact that overall survival is in itself high for breast cancer
raises concerns regarding some “non-inferiority” studies.
REFERENCES
1.	 Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA,
Black DM, Gilcrease MZ, et al. Improved axillary evaluation
following neoadjuvant therapy for patients with node-positive
breast cancer using seletive evaluation of clipped nodes:
Implementation of targeted axillary dissection. J Clin Oncol
2016;34:1072-8.
2.	 Caudle AS, Gonzalez-Angulo AM, Hunt KK, Pusztai L,
Kuerer HM, Mittendorf EA, et al. Impact of progression during
neoadjuvant chemotherapy on surgical management of breast
cancer. Ann Surg Oncol 2011;18:932-8.
3.	 Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant
systemic treatment in breast cancer: A meta-analysis. J Natl
Cancer Inst 2005;97:188-94.
4.	 Jimenez-Ballve A, Serrano-Palacio A, Garcia-Saenz JA,
Candil AO, Salsidua-Arroyo O, Román-Santamaría JM, et al.
Axillary pathologic response after neoadjuvant chemotherapy
in locally advanced breast cancer with axillary involvement.
Rev Esp Med Nucl Imagen Mol 2015;34:230-5.
5.	 Caudle AS, Yang WT, Mittendorf EA, Black DM, Hwang R,
Hobbs B, et al. Selective surgical localization of axillary lymph
nodes containing metastases in patients with breast cancer:
A prospective feasibility trial. JAMA Surg 2015;150:137-43.
6.	 Chang HR, Glaspy J, Allison MA, Kass FC, Elashoff R,
Chung DU, et al. Differential response of triple-negative
breast cancer to a docetaxel and carboplatin-based neoadjuvant
treatment. Cancer 2010;116:4227-37.
7.	 Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA,
et al. Response to neoadjuvant therapy and long-term survival
in patients with triple-negative breast cancer. J Clin Oncol
2008;26:1275-81.
8.	 Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM,
Wilke LG, Taback B, et al. Sentinel lymph node surgery after
neoadjuvant chemotherapy in patients with node-positive
breast cancer: The ACOSOG Z1071 (Alliance) clinical trial.
JAMA 2013;310:1455-61.
9.	 Prati R, Minami CA, Gornbein JA, Debruhl N,
Chung D, Chang HR, et al. Accuracy of clinical evaluation
of locally advanced breast cancer in patients receiving
neoadjuvant chemotherapy. Cancer 2009;115:1194-202.
10.	 PiñeroA, Gimenez J, Vidal-Sicart S, Intra M. Selective sentinel
lymph node biopsy and primary systemic therapy in breast
cáncer. Tumori 2010;96:17-23.
How to cite this article: Fernandez López, AJ, González
Valverde, FM. Confused Response to Neoadjuvant
Therapy in Breast Cancer. Clin J Surg 2018;1(1):20-21.
Figure 1: Hematoxylin and eosin stained section of tumor bed
showing macrometastasis and tumor-related capsular rupture

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Confused Response to Neoadjuvant Therapy in Breast Cancer

  • 1. Clinical Journal of Surgery  •  Vol 1  •  Issue 1  •  2018 20 INTRODUCTION N eoadjuvant chemotherapy (NAC) offers a series of advantages in patients with breast cancer, making it an important treatment option to be taken into account by multidisciplinary teams. Although a review of the current scientific evidence suggests its efficacy, the use of NAC remains highly variable.[1] Herein, we analyze our clinical experience with the use of NAC in a mammary ductal carcinoma, with the aim of helping multidisciplinary teams to identify patient suitability for neoadjuvant support. CASE REPORT We would like to contribute our experience regarding the findings in a 45-year-old female patient with a cochlear implant and no other relevant conditions who had a breast nodule identified during routine examination. The study showed a 12 mm tumor with evident axillary lymphadenopathy, which was found to be an infiltrating ductal carcinoma 100% estrogen receptor positive, 5% progesterone receptor positive, human epidermal growth factor receptor type 2 (HER2) negative, with Ki67 at 30%, and axillary metastasis. Following radiographic marking for both lesions, NAC was initiated (Adriamycin, cyclophosphamide, and docetaxel), which resulted in complete radiographic response (mammography and ultrasonography, since magnetic resonance imaging was unfeasible). During surgery, the tumor area was excised under harpoon guidance, and then, the clip-marked axillary lymphadenectomy was also removed and analyzed.The pathology study confirmed a complete pathological response (CPR) in both the breast and marked lymph node, but not in the rest of the axilla, where another lymph node developed macrometastasis and tumor-related capsular rupture [Figure 1]. DISCUSSION Progression during neoadjuvant therapy is a truly strange clinical finding even for a very experienced surgeon, with a rate of 3% in a meta-analysis of 1928 cases published by Caudle et al., in 2011.[2] In this case, response to NAC is seemingly inconsistent in the breast and the axilla for the same tumor. NAC facilitates surgery,assessesresponsetotherapy,andprovidesaprognostic factor more effectively than systemic therapy after surgery.[3-6] It is consequently very important for the specialized team CASE REPORT Confused Response to Neoadjuvant Therapy in Breast Cancer Antonio José Fernández López, Francisco Miguel González Valverde Department of Surgery, Pediatrics, Obstetrics and Gynecology, University of Murcia, Reina Sofía General University Hospital, Murcia, Spain ABSTRACT Neoadjuvant chemotherapy (NAC) brings a series of benefits for patients with mammary neoplasms. While literature shows its effectiveness, the utilization of NAC remains highly variable. Herein, we analyze our clinical experience with the use of NAC in an infiltrating ductal carcinoma with evident axillary lymphadenopathy. In this rare case, response to NAC is seemingly inconsistent in the breast and the axilla for the same tumor. Key words: Axillary macrometastasis, breast cancer, chemotherapy, neoadjuvant treatment, patient management Address for correspondence: Francisco Miguel González Valverde, C/Victorio 3, 2°C. 30003, Murcia, Spain. Phone: +34653571036. E-mail:  https://doi.org/10.33309/2639-9164.010107 www.asclepiusopen.com © 2018 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
  • 2. Fernandez López and González Valverde: Neoadjuvant therapy for breast cancer 21 Clinical Journal of Surgery  •  Vol 1  •  Issue 1  •  2018 to take into account the advantages and possible risks when selecting subjects who may gain from NAC. While extensive agreement exits regard the group of patients most likely to benefit from NAC, its use in clinical practice varies widely. In any case, a number of factors must be allowed for when selecting patients for NAC: • Patients presenting with inoperable locally advanced breast neoplasm • Young age • High tumor volume-to-breast ratio • All early-stage breast cancer patient, as they could probably benefit from NAC before surgery • Axillary lymph node-positive disease • Biological features of primitive cancer (positive HER2, high grade, hormone receptor negative, and triple- negative breast cancer). The efficacy of NAC is assessed by evaluating the clinical and radiological response during and after therapy and the pathological response after surgery. With nuances, CPR is defined as the complete clearance of the infiltrating component bothinthebreastandtheaxilla;hence,itrepresentsasignificant predictive factor for survival and disease-free interval.[7-9] CPR primarily depends on molecular phenotype. Good CPR rates are obtained in 31–60% of HER2 subtypes, 34–40% of triple-negative tumors, and 10% of luminal A and B types.[3,4,7] Furthermore, in luminal B tumors, CPR also depends on the Ki67 proliferation index and histologic grade; our patient had a high Ki67 at 30%. Both the sentinel node biopsy and clip-marked node biopsy offer a relevant number of false-negative results for axillary node metastasis after NAC.[1,10] Therefore, in the absence of comparative studies with adequate follow-up to provide true guidelines, potential residual disease in the axilla,[4,5] the effect of radiotherapy, and the impact of it all on overall survival make up the big enigma regarding breast cancer today. On the other hand, the fact that overall survival is in itself high for breast cancer raises concerns regarding some “non-inferiority” studies. REFERENCES 1. Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using seletive evaluation of clipped nodes: Implementation of targeted axillary dissection. J Clin Oncol 2016;34:1072-8. 2. Caudle AS, Gonzalez-Angulo AM, Hunt KK, Pusztai L, Kuerer HM, Mittendorf EA, et al. Impact of progression during neoadjuvant chemotherapy on surgical management of breast cancer. Ann Surg Oncol 2011;18:932-8. 3. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: A meta-analysis. J Natl Cancer Inst 2005;97:188-94. 4. Jimenez-Ballve A, Serrano-Palacio A, Garcia-Saenz JA, Candil AO, Salsidua-Arroyo O, Román-Santamaría JM, et al. Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement. Rev Esp Med Nucl Imagen Mol 2015;34:230-5. 5. Caudle AS, Yang WT, Mittendorf EA, Black DM, Hwang R, Hobbs B, et al. Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer: A prospective feasibility trial. JAMA Surg 2015;150:137-43. 6. Chang HR, Glaspy J, Allison MA, Kass FC, Elashoff R, Chung DU, et al. Differential response of triple-negative breast cancer to a docetaxel and carboplatin-based neoadjuvant treatment. Cancer 2010;116:4227-37. 7. Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008;26:1275-81. 8. Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: The ACOSOG Z1071 (Alliance) clinical trial. JAMA 2013;310:1455-61. 9. Prati R, Minami CA, Gornbein JA, Debruhl N, Chung D, Chang HR, et al. Accuracy of clinical evaluation of locally advanced breast cancer in patients receiving neoadjuvant chemotherapy. Cancer 2009;115:1194-202. 10. PiñeroA, Gimenez J, Vidal-Sicart S, Intra M. Selective sentinel lymph node biopsy and primary systemic therapy in breast cáncer. Tumori 2010;96:17-23. How to cite this article: Fernandez López, AJ, González Valverde, FM. Confused Response to Neoadjuvant Therapy in Breast Cancer. Clin J Surg 2018;1(1):20-21. Figure 1: Hematoxylin and eosin stained section of tumor bed showing macrometastasis and tumor-related capsular rupture