Breast carcinoma with spontaneous regression after needle biopsy: a case report and literature review
Case Report

Breast carcinoma with spontaneous regression after needle biopsy: a case report and literature review

Mahato Sasamoto1,2, Akimitsu Yamada1, Masanori Oshi1, Ikuko Ota2, Kenichi Yoshida2, Mayumi Yakeishi3, Yukio Tsuura3, Hidenobu Masui2, Itaru Endo1

1Department of Breast Surgery, Yokohama City University Hospital, Yokohama, Kanagawa, Japan; 2Department of Breast Surgery, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa, Japan; 3Department of Pathology, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa, Japan

Contributions: (I) Conception and design: All authors; (II) Administrative support: M Sasamoto, M Oshi; (III) Provision of study materials or patients: M Sasamoto; (IV) Collection and assembly of data: A Yamada, M Sasamoto; (V) Data analysis and interpretation: M Sasamoto, M Oshi; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Akimitsu Yamada, MD, PhD. Department of Breast Surgery, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ward, Yokohama, Kanagawa 236-0004, Japan. Email: ayamada@yokohama-cu.ac.jp.

Background: Spontaneous regression (SR) of cancer is a rare condition in which the cancer partially or completely disappears without treatment. We report a case of breast cancer with tumor regression and spontaneously induced T-cell-mediated immunological responses in a surgical specimen obtained after core needle biopsy (CNB).

Case Description: A 52-year-old woman presented with a mass in the right breast. Mammography showed a high-density mass with fine serrated margins in the right lower outer quadrant. Breast ultrasonography showed an irregular hypoechoic mass with a maximum diameter of 22 mm. CNB was performed and revealed an invasive ductal carcinoma with negative estrogen receptors, positive progesterone receptors, and negative HER2 (1+). The Ki67 index was 70% to 80%. Luminal B cT2N1M0 stage IIB right breast cancer was diagnosed. Although preoperative chemotherapy was considered, surgery was selected because of her history of schizophrenia. She underwent right mastectomy and axillary lymph node dissection. A postoperative pathological analysis revealed a 20 mm × 10 mm × 10 mm mass. However, most areas of the mass regressed and appeared as necrotic tissue with no obvious invasive areas. Only intraductal extension was observed in one glandular duct. Axillary lymph node metastases were not observed. These results suggest that the tumor may have spontaneously regressed, possibly because of the CNB procedure. Follow-up without treatment was performed, and no recurrence occurred during 2 years after surgery.

Conclusions: Invasive ductal carcinoma may spontaneously regress after preoperative CNB.

Keywords: Breast cancer; case report; CD8-positive T cell; core needle biopsy; spontaneous regression after needle biopsy

Submitted Oct 26, 2022. Accepted for publication Apr 17, 2023. Published online Jun 13, 2023.

doi: 10.21037/gs-22-629

Highlight box

Key findings

• We experienced a case of spontaneous regression due to stimulation of CNB and discussed the mechanism.

What is known and what is new?

• There have been several reports related to spontaneous regression of tumors, not only breast cancer, but the cause of spontaneous regression has not been elucidated.

• This report allowed us to discover a hypothesis regarding spontaneous tumor regression in breast cancer.

What is the implication, and what should change now?

• If the immune mechanisms involved in the spontaneous regression of tumors, as suggested in this study, are clarified in more detail, they may be useful for cancer prevention and new treatment methods.

Introduction

Spontaneous regression (SR) of malignant tumors is a rare condition defined as the partial or complete disappearance of the tumor with no treatment or with treatment that is not expected to reduce the tumor size (1,2). It is a phenomenon that can be observed regardless of the type of carcinoma, and its causes include needle biopsy. Recently, it was reported that immune responses occurring with cancer may be involved in the mechanisms of SR. We report a rare case of invasive ductal carcinoma of the breast that spontaneously regressed after core needle biopsy (CNB). We present this case in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-22-629/rc).

Case presentation

A 52-year-old woman presented to her primary physician because of a mass in the right breast. She had a history of schizophrenia and diabetes mellitus. She underwent hysterectomy for uterine cancer at age 51 years. She was using several medications, including ezetimibe, sitagliptin phosphate hydrate, metformin hydrochloride, glimepiride, perospirone hydrochloride, biperiden hydrochloride, mecobalamin, sultopride hydrochloride, and calcium sennoside A and B. Ultrasonography of the breast showed an irregular hypoechoic mass in the right breast, which was suspected to be breast cancer. The patient was referred to our department for further examination and treatment. Her body mass index was 30.8 kg/m2. She had no family history of breast or ovarian cancer. The physical examination revealed an elastic hard mass in the lower outer quadrant of the right breast without dimpling. Tumor marker levels were within normal limits [carcinoembryonic antigen (CEA), 3.7 ng/mL; carbohydrate antigen 15-3 (CA15-3), 10.3 U/mL; breast cancer antigen 225 (BCA225), 52.8 U/mL]. The mammogram showed that the breasts were heterogeneously dense, and that there was a round high-density mass with microlobulated margins in the outer-lower quadrant of the right breast (Figure 1). Breast ultrasonography revealed a round hypoechoic 22 mm × 17 mm × 22 mm mass with internal vascularity in the outer-lower quadrant of the right breast (Figure 2). The CNB results showed invasive ductal carcinoma of no special type that was grade 3, estrogen receptor (ER)-negative, progesterone receptor (PgR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative, with a Ki67 index of 70% to 80% (Figure 3).

Figure 1 Preoperative mammogram findings. (A) MLO; (B) CC. A lobulated, marginal, micro-serrated, hyperdense mass was observed in the right breast. MLO, mediolateral oblique view; CC, craniocaudal view; R, right; L, left.
Figure 2 Preoperative ultrasonography findings. (A) Ultrasonography at presentation. (B) Color Doppler imaging. There was a lobulated, hypoechoic, 22 mm × 17 mm × 22 mm mass with blood flow in the right breast.
Figure 3 Preoperative pathological findings. Core needle biopsy was performed to determine the histopathological findings of the right breast. (A) Hematoxylin and eosin (magnification ×200). (B) Immunohistochemistry study of the estrogen receptor (magnification ×200). (C) Immunohistochemistry study of the progesterone receptor (magnification ×200). (D) Immunohistochemistry study of human epidermal growth factor receptor 2 (magnification ×200). (E) Immunohistochemical study of Ki67 (magnification ×200).

Computed tomography was performed 13 days after CNB and showed an enhanced 22-mm mass in the right breast and an enlarged and enhanced lymph node in the right axilla. No other obvious distant metastases were observed (Figure 4).

Figure 4 Preoperative CT findings. CT with enhancement. (A) The 22-mm enhanced mass was in the area of the right breast. (B) A nonspecific enlarged lymph node was in the right axilla. CT, computed tomography.

Dynamic enhancement magnetic resonance imaging was performed 40 days after CNB and showed a homogeneously enhanced, round, irregular 22-mm mass in the outer-lower quadrant of the right breast. The time-intensity curve was fast-plateaued. No contralateral lesions were observed (Figure 5).

Figure 5 Preoperative MRI findings. (A) MRI with early gadolinium enhancement coronal section. (B) MRI with early gadolinium enhancement in the sagittal section. (C) Time-intensity curve. An enhanced 22-mm mass was observed in the right breast area. The time-intensity curve was fast-plateaued. MRI, magnetic resonance imaging; RoiA, region of interest analysis.

Based on these results, stage IIB breast cancer (cT2N1M0) was diagnosed. Although preoperative chemotherapy was considered as treatment, we decided to perform surgery because of her history of schizophrenia. She underwent right mastectomy and axillary lymph node dissection 48 days after CNB and was discharged on postoperative day 8.

Postoperative histopathology revealed that AE1/AE3-positive tumor cells did not observe in the region presumed to be the original tumor location; furthermore, tumor cells were replaced with necrotic tissue and lymphocyte infiltration was observed in the surrounding area. Tumor cells in the CNB specimen were not present in the postoperative specimen, suggesting the possibility of SR. CD8-positive cells were present in aggregated lymphocytes (Figure 6). The patient has been alive for more than 2 years without recurrence. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 6 Postoperative histopathological findings of the resected breast tissue are shown. Tumors were replaced with vitrified and necrotic tissue. Lymphocyte infiltration was observed in the surrounding area. (A) HE staining (magnification ×40). (B) HE staining (magnification ×200). An immunohistochemical analysis of immunological surface markers was performed. (C) AE1/AE3 (magnification ×200). (D) CD8 (magnification ×200). HE, hematoxylin and eosin.

Discussion

Breast cancer accounts for 43 (5.8%) of 741 cases of tumors with SR, which is relatively rare among carcinomas (3). Carcinomas that are prone to SR include renal cell carcinoma, neuroblastoma, malignant melanoma, hepatocellular carcinoma, and choriocarcinoma (4). These carcinomas are considered to have high immune activity, suggesting that immunological mechanisms are important factors in the mechanism of SR in cancer. Other mechanisms of SR in cancer have been assumed to include hormonal effects, tumor suppression by growth factors and cytokines, changes in the tumor growth environment, cell disruption, disruption of nutrient vessels, and altered healing response traits after biopsy (1,2). It has been speculated that these phenomena are related to trauma or infection (1,5). It has been reported that 28% of gynecological malignancies with SR occur after prolonged fever, and that sepsis may activate the patient’s immune response and enhance the immunity to the tumor (3,6). Our patient had no preoperative history of infection or trauma; however, lymphocytic infiltration and tumor necrosis were observed around the tumor, which was preoperatively treated with CNB. However, we found that CD8-positive cells were present in the postoperative specimen, which was undergone CNB. It is reported that surgical stimulation attracts immune cells and activate local immune responses (7). These attracted immune cells, especially anti-cancerous immune cells, induce the process of cancer cell killing, also known as “Immunogenic cell death (ICD)” (8). Given these mechanisms, we hypothesized that the stimulation of CNBs caused the SR in this case. Although ezetimibe, metformin, and glimepiride have been reported to have antitumor effects against breast cancer (9,10), the cancer appeared while the patient was using these drugs. Therefore, it is unlikely that these drugs were involved in SR of this tumor.

A literature search of the PubMed database using the keywords “spontaneous regression”, “spontaneous remission”, “breast cancer”, and “breast carcinoma” between 1994 and 2022 revealed nine reported cases, including autologous cases (Table 1) (4,5,11-17).

Table 1

Nine cases of breast cancer with SR

References Year Age (years)/sex Subtype Suggested mechanism Possible trigger Regression Pathologically verified SR
(11) 1994 46/F – Immunological response mediated by activated CD8+T cells and NK cells Treatment with dexamethasone Regression of primary tumor and metastatic lesion −
(5) 2008 68/F – Immunological and local inflammatory response Arm injury Needle biopsy Complete regression of primary tumor +
(4) 2014 52/F Luminal Immunological response Unclear Nearly complete regression of primary tumor and complete regression of metastatic lymph nodes +
(12) 2016 44/F Luminal Immunological response Needle biopsy Complete regression of primary tumor +
(13) 2019 67/F Luminal Immunological response Unclear Nearly complete regression of primary tumor and complete regression of metastatic lymph nodes +
(14) 2019 72/F TNBC Immunological response mediated by activated CD8+T cells Unclear Complete regression of primary tumor and metastatic lymph nodes +
(15) 2020 86/F TNBC Immunological response mediated by activated CD8+T cells Unclear Regression of metastatic skin lesions −
(16) 2020 70/M Luminal Ischemia/infarction Unclear Regression of primary tumor followed by reappearance −
(17) 2021 59/F TNBC Immunological response Unclear Partial regression of primary tumor +
Our case 2023 52/F Luminal Immunological response mediated by activated CD8+T cells Unclear Partial regression of primary tumor +

SR, spontaneous regression; NK, natural killer cells; TNBC, triple negative breast cancer.

Of the eight cases, excluding autopsy cases, seven SR cases were attributable to an immune response. Three of these studies have suggested the involvement of CD8-positive T cells. The mechanism by which cellular immunity acts against tumors is being elucidated, and tumor-infiltrating lymphocytes have been the focus of treatment, especially in breast cancer. Tumor cells express class I human leukocyte antigens on the cell membrane surface, which activate cytotoxic T cells to recognize tumor cells and exert antitumor effects (18). Furthermore, tumor-infiltrating lymphocyte activity is regulated by complex immune system activator and inhibitor pathways (19). Regarding our case, the pathological analysis revealed vitalization, necrotic tissue, and infiltration of CD8-positive lymphocytes in the tumor area, suggesting that an immune response may be involved in SR of the tumor. However, further studies are required to elucidate these mechanisms.

Whether SR is associated with the prognosis has not been adequately studied, and there are no clear criteria, such as the follow-up period. No recurrence was mentioned in any of the reports of breast cancer with SR. Our patient has not experienced recurrence, and it was recommended that she should undergo follow-up including mammography and ultrasonography annually for the next 8 years.

Conclusions

This case showed that invasive ductal carcinoma of the breast can experience SR after preoperative CNB. The exact mechanism of SR in cancer should be elucidated because it may lead to the development of cancer treatment and prevention.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-22-629/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-629/coif). AY serves as an unpaid editorial board member of Gland Surgery from April 2021 to March 2023. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Cole WH. Spontaneous regression of cancer and the importance of finding its cause. Natl Cancer Inst Monogr 1976;44:5-9. [PubMed]
  2. Cole WH. Efforts to explain spontaneous regression of cancer. J Surg Oncol 1981;17:201-9. [Crossref] [PubMed]
  3. Challis GB, Stam HJ. The spontaneous regression of cancer. A review of cases from 1900 to 1987. Acta Oncol 1990;29:545-50. [Crossref] [PubMed]
  4. Tokunaga E, Okano S, Nakashima Y, et al. Spontaneous regression of breast cancer with axillary lymph node metastasis: a case report and review of literature. Int J Clin Exp Pathol 2014;7:4371-80. [PubMed]
  5. Dussan C, Zubor P, Fernandez M, et al. Spontaneous regression of a breast carcinoma: a case report. Gynecol Obstet Invest 2008;65:206-11. [Crossref] [PubMed]
  6. Stephenson HE Jr, Delmez JA, Renden DI, et al. Host immunity and spontaneous regression of cancer evaluated by computerized data reduction study. Surg Gynecol Obstet 1971;133:649-55. [PubMed]
  7. Krysko DV, Garg AD, Kaczmarek A, et al. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 2012;12:860-75. [Crossref] [PubMed]
  8. Watkins MO, Tate AD, Lewis JS Jr, et al. Spontaneous Regression of Laryngeal Squamous Cell Carcinoma After Biopsy. Ear, Nose & Throat Journal 2022;101:59-62. [Crossref] [PubMed]
  9. Nowak C, Ärnlöv J. A Mendelian randomization study of the effects of blood lipids on breast cancer risk. Nat Commun 2018;9:3957. [Crossref] [PubMed]
  10. Long L, Hu X, Li X, et al. The Anti-Breast Cancer Effect and Mechanism of Glimepiride-Metformin Adduct. Onco Targets Ther 2020;13:3777-88. [Crossref] [PubMed]
  11. Maiche AG, Jekunen A, Rissanen P, et al. Sudden tumour regression with enhanced natural killer cell accumulation in a patient with stage IV breast cancer. Eur J Cancer 1994;30A:1642-6. [Crossref] [PubMed]
  12. Ito E, Nakano S, Otsuka M, et al. Spontaneous breast cancer remission: A case report. Int J Surg Case Rep 2016;25:132-6. [Crossref] [PubMed]
  13. Takayama S, Satomi K, Yoshida M, et al. Spontaneous regression of occult breast cancer with axillary lymph node metastasis: A case report. Int J Surg Case Rep 2019;63:75-9. [Crossref] [PubMed]
  14. Cserni G, Serfozo O, Ambrózay É, et al. Spontaneous pathological complete regression of high-grade triple-negative breast cancer with axillary metastasis. Pol J Pathol 2019;70:139-43. [Crossref] [PubMed]
  15. Tomasini C. Cytotoxic-mediated spontaneous regression of infammatory cutaneous metastases of breast carcinoma. J Cutan Pathol 2020;47:758-63. [Crossref] [PubMed]
  16. Katano K, Yoshimitsu Y, Kyuno T, et al. Temporary spontaneous regression of male breast cancer: a case report. Surg Case Rep 2020;6:311. [Crossref] [PubMed]
  17. Ohara M, Koi Y, Sasada T, et al. Spontaneous regression of breast cancer with immune response: a case report. Surg Case Rep 2021;7:10. [Crossref] [PubMed]
  18. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 2009;206:3015-29. [Crossref] [PubMed]
  19. Ali HR, Provenzano E, Dawson SJ, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol 2014;25:1536-43. [Crossref] [PubMed]
Cite this article as: Sasamoto M, Yamada A, Oshi M, Ota I, Yoshida K, Yakeishi M, Tsuura Y, Masui H, Endo I. Breast carcinoma with spontaneous regression after needle biopsy: a case report and literature review. Gland Surg 2023;12(6):853-859. doi: 10.21037/gs-22-629

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