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Late onset (22 years) of simultaneous tonsillar and cervical lymph node metastases from breast ductal carcinoma
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American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 627 – 630 www.elsevier.com/locate/amjoto
Late onset (22 years) of simultaneous tonsillar and cervical lymph node metastases from breast ductal carcinoma☆ Marco Maruzzo, MD a , Carlo Alberto Giorgi, MD a , Gino Marioni, MD b , Raffaele Bottin, MD c , Silvia Zanon, MD a , Filippo Marino, MD d , Haralabos Koussis, MD a,⁎ a
Operative Unit of Medical Oncology 2 Unit, IRCCS IOV, Padova, Italy Department of Neurosciences, Otolaryngology Section, Padova University Hospital, Padova, Italy c Department of Neurosciences, Oto-Surgery Section, Padova University Hospital, Padova, Italy d Department of Medical/Diagnostic Sciences and Special Therapies, Anatomic Pathology Section, Padova University Hospital, Padova, Italy Received 28 January 2012 b
Abstract
Breast cancer is the leading cause of cancer-related mortality in women worldwide; the most common metastatic sites are lymph nodes, lung, liver, and brain. Tonsil metastases from breast cancer are extremely rare. Herein, we report a case of a 74-year-old woman with simultaneous occurrence of tonsillar and cervical lymph nodes metastases after a disease-free interval of 22 years. © 2012 Elsevier Inc. All rights reserved.
Breast cancer is the leading cause of cancer-related mortality in women worldwide, representing approximately 23% of all cancer diagnosis and 14% of all death causes in females in 2008 [1], with approximately 1.4 million estimated new cases per year [2]. The most common metastatic sites are lungs (42%–58%), liver (48%–55%), bone (20%–43%), pleura (31%–41%), and less frequently, skin, brain, kidney, stomach, uterus, and spleen [3]. In general, tonsils are an unusual site of metastasis with an occurrence rate lower than 1% of all metastatic sites. In particular, tonsil metastases from breast cancer are extremely rare. Cervical lymph node metastases due to breast carcinoma are unusual [4] but described also in the contralateral side of the neck [5]. In this report, we described a rare case of late (22 years) simultaneous occurrence of tonsillar and neck lymph node metastases from breast cancer. 1. Case report In March 2010, a 74-year-old woman complaining oropharyngeal discomfort and right neck swelling underwent ENT evaluation followed by a contrast-enhanced computed ☆
Conflict of interest/financial disclosure: none. ⁎ Corresponding author. Medical Oncology 2 Unit, Istituto Oncologico Veneto IOV IRCCS, Via Gattamelata 64, I-35128 Padova, Italy. E-mail address: [email protected] (H. Koussis). 0196-0709/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjoto.2012.02.003
tomography, which revealed right tonsil and ipsilateral cervical lymph node swelling. A tonsillar biopsy was performed under topical anesthesia; histopathologic evaluation was consistent in localization of carcinoma, which consists of elements of medium size, nucleolus, often in cell division. The patient underwent extended right tonsillectomy and ipsilateral modified radical neck dissection type III. Final histologic examination concluded that tonsillar lesion was consistent with the secondary localization of a mammary carcinoma (Fig. 1); furthermore, 2 of 15 lymph nodes examined were involved by breast cancer (Fig.1). Further immunohistochemical examination on tonsillar and lymph nodal tissue has been performed, revealing positive estrogen receptor (ER, 80%) [Fig. 1], progesterone receptor (PR, 25%), and Ki-67 (30%) staining. Human epidermal growth factor receptor 2 (HER-2/neu) resulted overexpressed (score 3+) in tonsillar and lymph nodal localization. In April 2010, the patient, in good general condition (ECOG PS = 0), was referred to the Medical Oncology 2 Department, Istituto Oncologico Veneto IOV IRCCS. At admission, a complete patient's medical history had been collected, revealing that the patient had undergone left breast external superior quadrantectomy in 1987 because of breast carcinoma (ductal infiltrative carcinoma, staged as pT1b N0 M0, G3, ER negative, PR negative; Ki67 not assessed; HER2/neu not assessed because its role was not known at the time). Because of the aforementioned carcinoma extension,
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M. Maruzzo et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 627–630
Fig. 1. (A) Tonsillar localization of breast carcinoma (hematoxylin and eosin, original magnification ×200). (B) Breast carcinoma tonsillar localization, higher magnification (hematoxylin and eosin, original magnification ×400). (C) Cervical lymph node localization of breast carcinoma (hematoxylin and eosin, original magnification ×100). (D) Positive nuclear ER in tonsillar localization of breast carcinoma (original magnification ×400).
the patient had undergone adjuvant radiotherapy and serial follow-up controls for more than 20 years in another cancer center. A histopathologic revision of the specimen from the quadrantectomy performed in 1987 was required; the previous diagnosis of ductal infiltrative carcinoma was confirmed. Immunohistochemical reevaluation showed no ER or PR expression; Ki67 was also negative, and HER2/neu was not overexpressed. After head and neck surgery, the patient performed a positron emission tomographic/computed tomographic scan revealing no pathologic areas of significant metabolic uptake. The patient refused any infusive treatments, including proposed targeted therapy based on trastuzumab. Although positive PR expression was a favorable prognostic factor (even if with a low percentage of expression), HER2/neu overexpression lean toward an aggressive tumor. Respecting patient's decision and according to the positivity of PR
expression, an aromatase inhibitor–based adjuvant therapy was proposed (letrozole, 2.5 mg/d for 5 years); the patient began the treatment in May 2010. Nowadays (January 2012), therapy is still ongoing and well tolerated with the patient showing no evidence of recurrent disease. 2. Discussion Metastatic tumors to the tonsil represent less than 1% of all tonsillar tumors [6,7]. To the best of our knowledge, less than 10 cases of tonsillar metastasis from breast cancer have been reported, with at least 3 cases described before 1910 [8-11]. In breast cancer, late-onset metastases are often associated to a better prognosis than early recurrence [12]. On the other hand, tonsillar metastases seem to carry a poor prognosis regardless of the primary tumor [13].
M. Maruzzo et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 627–630
It is well known that neck lymph node metastases do not exclusively derive from head and neck primary cancers [14,15]. Reviewing literature, neck metastases from breast cancer are reported as supraclavicular lymph node metastases. According to the more recent version of American Joint Committee on Cancer Staging System [16], all breast cancer metastases located superiorly to supraclavicular fossa should be considered as distant metastases (M1). Considering 3170 patients with primary breast cancer treated in the period of 1990 to 1999, Chen et al [4] reported 63 patients with isolated supraclavicular lymph node metastasis. Analyzing in detail 12 original cases of neck metastasis due to breast carcinoma, Sesterhenn et al [17] found that neck level V was the area where most of the metastases were located (8/12), followed by level IV (7/12), level III (6/12), and level II (1/12). Although in current classifications, the supraclavicular region corresponds to neck level IV and the distal part of level V, and in contrast, levels III and II do not belong to the regular lymphatic drainage system of the breast, the authors found that, in all cases with metastases located at level III, positive lymph nodes at level IV were found [17]. This evidence supported the hypothesis that the differentiation between lymph node locoregional disease and distant metastases from breast cancer above the clavicle could be debated on. In our case, it was not possible to determine the lymph nodal level of the metastatic localizations; we can only assert that the neck dissection included the lymph nodes from level II to V, not enabling to trace more accurately the lymph nodal site of metastasis. The occurrence of breast cancer metastases after several years of disease-free survival is uncommon [11,18,19]. In the present case, the way of metastatic disease presentation was peculiar because, considering the very late occurrence, it likely interested first the tonsil and then the ipsilateral regional lymph nodes. A late carcinoma recurrence may be due to cancer cells being in a dormant state (prolonged state of G0); tumor dormancy has been recognized as a clinical phenomenon in numerous types of cancer [20]. Circulating breast cancer cells have been detected in patients up to 20 years after primary diagnosis [21], even in the absence of evident disease. The stimuli for triggering the regrowth of dormant cells are unclear but could include immunologic factors, local tissue injury, and other yet unidentified causes [22,23]. This quiescence is likely to afford protection from many cytotoxic drugs, which only targets actively the cycling cells [3]. The theories outlined above can very well explain the 22-year period before tonsillar and lymphatic metastases occurrence in the present case of breast carcinoma. Considering the results of our immunohistochemical reevaluation of the breast carcinoma (lack of expression of ERs and PRs as well as absence of HER2/neu overexpression), the patient showed a primary cancer that belongs to the specific subgroup called triple-negative breast cancer (TNBC) [24]. Triple-negative breast cancer accounts approximately for 15% to 20% of all breast cancer. Because of this expression profile, this subgroup of tumors is
629
not amenable to treatment neither with hormone therapy nor anti-Her2 monoclonal antibodies. Triple-negative breast cancer has earlier relapse and more frequently visceral metastasis than other breast cancers and rapid disease progression [25,26]. However, patients with TNBC who are disease free 5 years after treatment have a recurrence risk equal to that of other histologic types. Analyzing immunohistochemically the distant recurrences, our patient showed HER-2 overexpression and positive PR. These differences between metastatic and primary breast carcinoma phenotype have been previously described: the change in HER2/neu expression has been up to 33.2%, whereas the change of expression in hormonal receptors has been up to 20% [27,28]. Because of this fact, it is recommended to obtain a metastasis' biopsy before treatment institution to evaluate cancer characteristics. A rational recurrence's treatment is related to neoplasm characteristics (ER, PR, HER2/neu, Ki67 expression), site of metastasis (visceral vs bone metastasis), disease-free survival, and any previous therapeutic approach. HER2/neu amplification or overexpression is an important marker of aggressive disease, and it is associated to a poor prognosis [29]. Specific molecular target therapies have been developed for this disease setting, such as trastuzumab, lapatinib, or neratinib. The standard treatment for HER2/neu-positive metastatic breast cancer is the association of trastuzumab with conventional chemotherapy. However, in our case, head and neck metastases were radically removed by surgery, and the patient decided not to receive adjuvant trastuzumab with or without chemotherapy, probably because she was encouraged by the long well-being period after primary surgery. We can hypothesize that, in our patient, the primary TNBC might have a less aggressive clinical behavior than usual because of a low Ki67 expression (as recently reported in Keam et al [30]); unfortunately, this theory is impossible to be confirmed considering that Ki67 reevaluation on primary breast carcinoma was not positive probably because of the long-term (22 years) storage in paraffin of the archival tissue. It is reasonable that, for the same reason, also the determination of HER2/neu status of primary cancer could not be reliable. Although the present case has to be considered a rare occurrence, it confirms that sometimes a patient may result as clinically cured but not biologically free of cancer; long-term follow-up periods have to be always recommended. In addition, in late onset of distant metastases due to breast carcinoma, it is advisable to obtain a tissue biopsy from the recurrent lesion to evaluate the histologic and biochemical parameters necessary to plan a rational treatment approach. References [1] Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90. [2] Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
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[3] Al-Benna S, Tzakas E. Submental lymph node metastasis from invasive ductal breast carcinoma. Arch Gynecol Obstet 2012;285:1153-6. [4] Chen SC, Chang HK, Lin YC, et al. Prognosis of breast cancer after supraclavicular lymph node metastasis: not a distant metastasis. Ann Surg Oncol 2006;13:1457-65. [5] Harlak A, Karahatay S, Onguru O, et al. Chyle fistula after neck dissection for an unusual breast cancer recurrence. Breast Care 2008;3: 274-6. [6] Crawford BE, Callihan MD, Corio RL, et al. Oral pathology. Otolaryngol Clin North Am 1979;12:29-43. [7] Eisenkraft BL, Som PM. The spectrum of benign and malignant etiologies of cervical node calcification. AJR Am J Roentgenol 1999; 172:1433-7. [8] Willis RA. Secondary tumours in sundry unusual situations. In: Willis RA, editor. The spread of tumours in the human body. London: Butterworth; 1973. p. 279-95. [9] Barton TK, Kesterson GH, Wellman D, et al. Tonsillar metastasis from carcinoma of the breast with ultrastructural and steroid receptor analyses. Laryngoscope 1980;90:477-85. [10] Lee KJ, Fischer DS, Fappiano AP. Breast carcinoma metastatic to the palatine tonsils. Conn Med 1987;51:76-9. [11] Tueche SG, Nguyen H, Larsimont D, et al. Late onset of tonsillar metastasis from breast cancer. Eur J Surg Oncol 1999;25:439-40. [12] Demicheli R, Abbattista A, Miceli R, et al. Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy. Breast Cancer Res Treat 1996;41:177-85. [13] Brownson RJ, Jaques WE, LaMonte SE, et al. Hypernephroma metastatic to the palatine tonsils. Ann Otol Rhinol Laryngol 1979;88: 235-40. [14] Kruk-Zagajewska A, Szmeja Z, Wierzbicka M. Neck metastases from unknown primary neoplasms (CUP syndrome). Otolaryngol Pol 2000; 54(Suppl 31):262-6. [15] Singletary SE, Allred C, Ashley P, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002;20:3628-36.
[16] Edge SB, Byrd DR, Compton CC, et al. AJCC (American Joint Committee on Cancer). Cancer Staging Manual, 7th edition. New York: Springer-Verlag; 2010. [17] Sesterhenn AM, Albert US, Barth PJ, et al. The status of neck node metastases in breast cancer-loco-regional or distant. Breast 2006;15:181-6. [18] Mamby CC, Love RR, Heaney E. Metastatic breast cancer 39 years after primary treatment. Wis Med J 1993;92:567-9. [19] Dal Lago D, Villa G, Miguoli R, et al. An unusual case of breast cancer relapse after 30 years of disease-free survival. Age Ageing 1998;27: 649-50. [20] Goss PE, Chambers AF. Does tumour dormancy offer a therapeutic target? Nat Rev Cancer 2010;10:871-7. [21] Meng S, Tripathy D, Frenkel EP, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 2004;10:8152-62. [22] Kendal WS. Chance mechanisms affecting the burden of metastases. BMC Cancer 2005;5:138. [23] Chambers AF. Influence of diet on metastasis and tumor dormancy. Clin Exp Metastasis 2009;26:61-6. [24] Barrett SV. Breast cancer. J R Coll Physicians 2010;40:335-8. [25] Perez EA, Patel T, Moreno-Aspitia A. Efficacy of ixabepilone in ER/PR/HER2-negative (triple-negative) breast cancer. Breast Cancer Res Treat 2010;121:261-71. [26] Isakoff SJ. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J 2010;16:53-61. [27] Guarneri V, Giovannelli S, Ficarra G, et al. Comparison of HER-2 and hormone receptor expression in primary breast cancers and asynchronous paired metastases: impact on patient management. Oncologist 2008;13:838-44. [28] Santinelli A, Pisa E, Stramazzotti D, et al. HER-2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy. Int J Cancer 2008;122:999-1044. [29] Gutierrez C, Schiff R. HER2: biology, detection, and clinical implications. Arch Pathol Lab Med 2011;135:55-62. [30] Keam B, Im S, Lee K, et al. Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Res 2011;13:R22.
American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 627 – 630 www.elsevier.com/locate/amjoto
Late onset (22 years) of simultaneous tonsillar and cervical lymph node metastases from breast ductal carcinoma☆ Marco Maruzzo, MD a , Carlo Alberto Giorgi, MD a , Gino Marioni, MD b , Raffaele Bottin, MD c , Silvia Zanon, MD a , Filippo Marino, MD d , Haralabos Koussis, MD a,⁎ a
Operative Unit of Medical Oncology 2 Unit, IRCCS IOV, Padova, Italy Department of Neurosciences, Otolaryngology Section, Padova University Hospital, Padova, Italy c Department of Neurosciences, Oto-Surgery Section, Padova University Hospital, Padova, Italy d Department of Medical/Diagnostic Sciences and Special Therapies, Anatomic Pathology Section, Padova University Hospital, Padova, Italy Received 28 January 2012 b
Abstract
Breast cancer is the leading cause of cancer-related mortality in women worldwide; the most common metastatic sites are lymph nodes, lung, liver, and brain. Tonsil metastases from breast cancer are extremely rare. Herein, we report a case of a 74-year-old woman with simultaneous occurrence of tonsillar and cervical lymph nodes metastases after a disease-free interval of 22 years. © 2012 Elsevier Inc. All rights reserved.
Breast cancer is the leading cause of cancer-related mortality in women worldwide, representing approximately 23% of all cancer diagnosis and 14% of all death causes in females in 2008 [1], with approximately 1.4 million estimated new cases per year [2]. The most common metastatic sites are lungs (42%–58%), liver (48%–55%), bone (20%–43%), pleura (31%–41%), and less frequently, skin, brain, kidney, stomach, uterus, and spleen [3]. In general, tonsils are an unusual site of metastasis with an occurrence rate lower than 1% of all metastatic sites. In particular, tonsil metastases from breast cancer are extremely rare. Cervical lymph node metastases due to breast carcinoma are unusual [4] but described also in the contralateral side of the neck [5]. In this report, we described a rare case of late (22 years) simultaneous occurrence of tonsillar and neck lymph node metastases from breast cancer. 1. Case report In March 2010, a 74-year-old woman complaining oropharyngeal discomfort and right neck swelling underwent ENT evaluation followed by a contrast-enhanced computed ☆
Conflict of interest/financial disclosure: none. ⁎ Corresponding author. Medical Oncology 2 Unit, Istituto Oncologico Veneto IOV IRCCS, Via Gattamelata 64, I-35128 Padova, Italy. E-mail address: [email protected] (H. Koussis). 0196-0709/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjoto.2012.02.003
tomography, which revealed right tonsil and ipsilateral cervical lymph node swelling. A tonsillar biopsy was performed under topical anesthesia; histopathologic evaluation was consistent in localization of carcinoma, which consists of elements of medium size, nucleolus, often in cell division. The patient underwent extended right tonsillectomy and ipsilateral modified radical neck dissection type III. Final histologic examination concluded that tonsillar lesion was consistent with the secondary localization of a mammary carcinoma (Fig. 1); furthermore, 2 of 15 lymph nodes examined were involved by breast cancer (Fig.1). Further immunohistochemical examination on tonsillar and lymph nodal tissue has been performed, revealing positive estrogen receptor (ER, 80%) [Fig. 1], progesterone receptor (PR, 25%), and Ki-67 (30%) staining. Human epidermal growth factor receptor 2 (HER-2/neu) resulted overexpressed (score 3+) in tonsillar and lymph nodal localization. In April 2010, the patient, in good general condition (ECOG PS = 0), was referred to the Medical Oncology 2 Department, Istituto Oncologico Veneto IOV IRCCS. At admission, a complete patient's medical history had been collected, revealing that the patient had undergone left breast external superior quadrantectomy in 1987 because of breast carcinoma (ductal infiltrative carcinoma, staged as pT1b N0 M0, G3, ER negative, PR negative; Ki67 not assessed; HER2/neu not assessed because its role was not known at the time). Because of the aforementioned carcinoma extension,
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M. Maruzzo et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 627–630
Fig. 1. (A) Tonsillar localization of breast carcinoma (hematoxylin and eosin, original magnification ×200). (B) Breast carcinoma tonsillar localization, higher magnification (hematoxylin and eosin, original magnification ×400). (C) Cervical lymph node localization of breast carcinoma (hematoxylin and eosin, original magnification ×100). (D) Positive nuclear ER in tonsillar localization of breast carcinoma (original magnification ×400).
the patient had undergone adjuvant radiotherapy and serial follow-up controls for more than 20 years in another cancer center. A histopathologic revision of the specimen from the quadrantectomy performed in 1987 was required; the previous diagnosis of ductal infiltrative carcinoma was confirmed. Immunohistochemical reevaluation showed no ER or PR expression; Ki67 was also negative, and HER2/neu was not overexpressed. After head and neck surgery, the patient performed a positron emission tomographic/computed tomographic scan revealing no pathologic areas of significant metabolic uptake. The patient refused any infusive treatments, including proposed targeted therapy based on trastuzumab. Although positive PR expression was a favorable prognostic factor (even if with a low percentage of expression), HER2/neu overexpression lean toward an aggressive tumor. Respecting patient's decision and according to the positivity of PR
expression, an aromatase inhibitor–based adjuvant therapy was proposed (letrozole, 2.5 mg/d for 5 years); the patient began the treatment in May 2010. Nowadays (January 2012), therapy is still ongoing and well tolerated with the patient showing no evidence of recurrent disease. 2. Discussion Metastatic tumors to the tonsil represent less than 1% of all tonsillar tumors [6,7]. To the best of our knowledge, less than 10 cases of tonsillar metastasis from breast cancer have been reported, with at least 3 cases described before 1910 [8-11]. In breast cancer, late-onset metastases are often associated to a better prognosis than early recurrence [12]. On the other hand, tonsillar metastases seem to carry a poor prognosis regardless of the primary tumor [13].
M. Maruzzo et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 627–630
It is well known that neck lymph node metastases do not exclusively derive from head and neck primary cancers [14,15]. Reviewing literature, neck metastases from breast cancer are reported as supraclavicular lymph node metastases. According to the more recent version of American Joint Committee on Cancer Staging System [16], all breast cancer metastases located superiorly to supraclavicular fossa should be considered as distant metastases (M1). Considering 3170 patients with primary breast cancer treated in the period of 1990 to 1999, Chen et al [4] reported 63 patients with isolated supraclavicular lymph node metastasis. Analyzing in detail 12 original cases of neck metastasis due to breast carcinoma, Sesterhenn et al [17] found that neck level V was the area where most of the metastases were located (8/12), followed by level IV (7/12), level III (6/12), and level II (1/12). Although in current classifications, the supraclavicular region corresponds to neck level IV and the distal part of level V, and in contrast, levels III and II do not belong to the regular lymphatic drainage system of the breast, the authors found that, in all cases with metastases located at level III, positive lymph nodes at level IV were found [17]. This evidence supported the hypothesis that the differentiation between lymph node locoregional disease and distant metastases from breast cancer above the clavicle could be debated on. In our case, it was not possible to determine the lymph nodal level of the metastatic localizations; we can only assert that the neck dissection included the lymph nodes from level II to V, not enabling to trace more accurately the lymph nodal site of metastasis. The occurrence of breast cancer metastases after several years of disease-free survival is uncommon [11,18,19]. In the present case, the way of metastatic disease presentation was peculiar because, considering the very late occurrence, it likely interested first the tonsil and then the ipsilateral regional lymph nodes. A late carcinoma recurrence may be due to cancer cells being in a dormant state (prolonged state of G0); tumor dormancy has been recognized as a clinical phenomenon in numerous types of cancer [20]. Circulating breast cancer cells have been detected in patients up to 20 years after primary diagnosis [21], even in the absence of evident disease. The stimuli for triggering the regrowth of dormant cells are unclear but could include immunologic factors, local tissue injury, and other yet unidentified causes [22,23]. This quiescence is likely to afford protection from many cytotoxic drugs, which only targets actively the cycling cells [3]. The theories outlined above can very well explain the 22-year period before tonsillar and lymphatic metastases occurrence in the present case of breast carcinoma. Considering the results of our immunohistochemical reevaluation of the breast carcinoma (lack of expression of ERs and PRs as well as absence of HER2/neu overexpression), the patient showed a primary cancer that belongs to the specific subgroup called triple-negative breast cancer (TNBC) [24]. Triple-negative breast cancer accounts approximately for 15% to 20% of all breast cancer. Because of this expression profile, this subgroup of tumors is
629
not amenable to treatment neither with hormone therapy nor anti-Her2 monoclonal antibodies. Triple-negative breast cancer has earlier relapse and more frequently visceral metastasis than other breast cancers and rapid disease progression [25,26]. However, patients with TNBC who are disease free 5 years after treatment have a recurrence risk equal to that of other histologic types. Analyzing immunohistochemically the distant recurrences, our patient showed HER-2 overexpression and positive PR. These differences between metastatic and primary breast carcinoma phenotype have been previously described: the change in HER2/neu expression has been up to 33.2%, whereas the change of expression in hormonal receptors has been up to 20% [27,28]. Because of this fact, it is recommended to obtain a metastasis' biopsy before treatment institution to evaluate cancer characteristics. A rational recurrence's treatment is related to neoplasm characteristics (ER, PR, HER2/neu, Ki67 expression), site of metastasis (visceral vs bone metastasis), disease-free survival, and any previous therapeutic approach. HER2/neu amplification or overexpression is an important marker of aggressive disease, and it is associated to a poor prognosis [29]. Specific molecular target therapies have been developed for this disease setting, such as trastuzumab, lapatinib, or neratinib. The standard treatment for HER2/neu-positive metastatic breast cancer is the association of trastuzumab with conventional chemotherapy. However, in our case, head and neck metastases were radically removed by surgery, and the patient decided not to receive adjuvant trastuzumab with or without chemotherapy, probably because she was encouraged by the long well-being period after primary surgery. We can hypothesize that, in our patient, the primary TNBC might have a less aggressive clinical behavior than usual because of a low Ki67 expression (as recently reported in Keam et al [30]); unfortunately, this theory is impossible to be confirmed considering that Ki67 reevaluation on primary breast carcinoma was not positive probably because of the long-term (22 years) storage in paraffin of the archival tissue. It is reasonable that, for the same reason, also the determination of HER2/neu status of primary cancer could not be reliable. Although the present case has to be considered a rare occurrence, it confirms that sometimes a patient may result as clinically cured but not biologically free of cancer; long-term follow-up periods have to be always recommended. In addition, in late onset of distant metastases due to breast carcinoma, it is advisable to obtain a tissue biopsy from the recurrent lesion to evaluate the histologic and biochemical parameters necessary to plan a rational treatment approach. References [1] Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90. [2] Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
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M. Maruzzo et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 627–630
[3] Al-Benna S, Tzakas E. Submental lymph node metastasis from invasive ductal breast carcinoma. Arch Gynecol Obstet 2012;285:1153-6. [4] Chen SC, Chang HK, Lin YC, et al. Prognosis of breast cancer after supraclavicular lymph node metastasis: not a distant metastasis. Ann Surg Oncol 2006;13:1457-65. [5] Harlak A, Karahatay S, Onguru O, et al. Chyle fistula after neck dissection for an unusual breast cancer recurrence. Breast Care 2008;3: 274-6. [6] Crawford BE, Callihan MD, Corio RL, et al. Oral pathology. Otolaryngol Clin North Am 1979;12:29-43. [7] Eisenkraft BL, Som PM. The spectrum of benign and malignant etiologies of cervical node calcification. AJR Am J Roentgenol 1999; 172:1433-7. [8] Willis RA. Secondary tumours in sundry unusual situations. In: Willis RA, editor. The spread of tumours in the human body. London: Butterworth; 1973. p. 279-95. [9] Barton TK, Kesterson GH, Wellman D, et al. Tonsillar metastasis from carcinoma of the breast with ultrastructural and steroid receptor analyses. Laryngoscope 1980;90:477-85. [10] Lee KJ, Fischer DS, Fappiano AP. Breast carcinoma metastatic to the palatine tonsils. Conn Med 1987;51:76-9. [11] Tueche SG, Nguyen H, Larsimont D, et al. Late onset of tonsillar metastasis from breast cancer. Eur J Surg Oncol 1999;25:439-40. [12] Demicheli R, Abbattista A, Miceli R, et al. Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy. Breast Cancer Res Treat 1996;41:177-85. [13] Brownson RJ, Jaques WE, LaMonte SE, et al. Hypernephroma metastatic to the palatine tonsils. Ann Otol Rhinol Laryngol 1979;88: 235-40. [14] Kruk-Zagajewska A, Szmeja Z, Wierzbicka M. Neck metastases from unknown primary neoplasms (CUP syndrome). Otolaryngol Pol 2000; 54(Suppl 31):262-6. [15] Singletary SE, Allred C, Ashley P, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002;20:3628-36.
[16] Edge SB, Byrd DR, Compton CC, et al. AJCC (American Joint Committee on Cancer). Cancer Staging Manual, 7th edition. New York: Springer-Verlag; 2010. [17] Sesterhenn AM, Albert US, Barth PJ, et al. The status of neck node metastases in breast cancer-loco-regional or distant. Breast 2006;15:181-6. [18] Mamby CC, Love RR, Heaney E. Metastatic breast cancer 39 years after primary treatment. Wis Med J 1993;92:567-9. [19] Dal Lago D, Villa G, Miguoli R, et al. An unusual case of breast cancer relapse after 30 years of disease-free survival. Age Ageing 1998;27: 649-50. [20] Goss PE, Chambers AF. Does tumour dormancy offer a therapeutic target? Nat Rev Cancer 2010;10:871-7. [21] Meng S, Tripathy D, Frenkel EP, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 2004;10:8152-62. [22] Kendal WS. Chance mechanisms affecting the burden of metastases. BMC Cancer 2005;5:138. [23] Chambers AF. Influence of diet on metastasis and tumor dormancy. Clin Exp Metastasis 2009;26:61-6. [24] Barrett SV. Breast cancer. J R Coll Physicians 2010;40:335-8. [25] Perez EA, Patel T, Moreno-Aspitia A. Efficacy of ixabepilone in ER/PR/HER2-negative (triple-negative) breast cancer. Breast Cancer Res Treat 2010;121:261-71. [26] Isakoff SJ. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J 2010;16:53-61. [27] Guarneri V, Giovannelli S, Ficarra G, et al. Comparison of HER-2 and hormone receptor expression in primary breast cancers and asynchronous paired metastases: impact on patient management. Oncologist 2008;13:838-44. [28] Santinelli A, Pisa E, Stramazzotti D, et al. HER-2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy. Int J Cancer 2008;122:999-1044. [29] Gutierrez C, Schiff R. HER2: biology, detection, and clinical implications. Arch Pathol Lab Med 2011;135:55-62. [30] Keam B, Im S, Lee K, et al. Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Res 2011;13:R22.