- Email: [email protected]
Second Primary Ipsilateral Breast Cancer With Contralateral Axillary Involvement: A Case Report and Literature Review
Case Report
Second Primary Ipsilateral Breast Cancer With Contralateral Axillary Involvement: A Case Report and Literature Review Christina I. Herold,1 Elizabeth M. Gaughan,1 Carolyn C. Lamb,2 Nadine M. Tung1 Clinical Practice Points ●
●
After breast-conserving surgery for an initial breast cancer, the incidence of lymphatic drainage to sites other than the ipsilateral axilla, such as the contralateral axilla, increases significantly at the time of a second primary ipsilateral breast cancer. Given the likelihood of altered lymphatic drainage, and in the absence of distant metastatic sites, consideration should be given to treating patients with a second primary ipsilateral breast cancer and con-
●
tralateral axillary lymph node involvement with curative intent. This clinical issue may become more common as the incidence of second primary ipsilateral breast cancer would be expected to increase due to widespread adoption of breast-conserving surgery, improved prognosis for patients with an initial early-stage breast cancer, and highly sensitive screening modalities such as magnetic resonance imaging.
Clinical Breast Cancer, Vol. 11, No. 6, 406-8 © 2011 Elsevier Inc. All rights reserved. Keywords: Ipsilateral breast tumor recurrence, Second primary ipsilateral breast cancer, Sentinel lymph node biopsy
Introduction The significance of contralateral axillary tumor involvement at the time of a new breast cancer diagnosis is not clear. Whether to treat such patients with curative intent, if staging workup for distant metastatic disease is negative, is not known. We report a case of a woman with a second primary ipsilateral breast cancer who presented with contralateral lymph node involvement. The literature evaluating lymphatic drainage of breast cancers to sites other than the ipsilateral axilla is reviewed. Particular attention is paid to whether such drainage is altered by previous breast and/or axillary surgery in the setting of either a new ipsilateral breast primary or ipsilateral breast tumor recurrence (IBTR).
Case Report In 2000, at the age of 22 years, the patient presented with a palpable lesion in the axillary tail of her left breast. She underwent left breast-conserving surgery (BCS) and axillary lymph node dissection 1 Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 2 Division of Radiation Oncology, Mt. Auburn Hospital, Cambridge, MA
Submitted: Jun 23, 2011; Accepted: Jun 27, 2011 Address for correspondence: Christina I. Herold, MD, Beth Israel Deaconess Medical Center, 330 Brookline Ave, KS-108C, Boston, MA 02215 Tel: 617-667-1970; Fax: 617-667-1960; e-mail contact: [email protected]
406
Clinical Breast Cancer December 2011
(ALND). Pathology showed a 1.5-cm poorly differentiated invasive ductal carcinoma that was estrogen receptor (ER)-negative and lacked over-expression of human epidermal growth factor receptor 2 (HER-2) by immunohistochemistry (IHC); 11 lymph nodes showed no evidence of metastatic disease. In the adjuvant setting she was treated with four cycles of doxorubicin and cyclophosphamide followed by radiation therapy to the whole breast (180 cGy ⫻ 25) and a boost to the axillary tail tumor bed for an additional 16 Gy. She was subsequently followed-up every 6 months with clinical examinations as well as breast surveillance with alternating mammography and magnetic resonance imaging (MRI) of the breast. In 2009, at the age of 31 years, interval screening mammography revealed new calcifications in the deep medial aspect of the patient’s left breast (Figure 1). Core biopsy was diagnostic of invasive ductal carcinoma. This tumor was believed to represent a second primary breast cancer of the left breast because it was located in a different quadrant and occurred 9 years from the initial cancer. The patient subsequently reported contralateral right axillary pain and fullness which was confirmed by physical examination and breast imaging (Figure 2). Fine-needle aspiration of an enlarged right axillary node confirmed metastatic carcinoma. Right breast imaging was significant only for malignant axillary lymphadenopathy; there were no other abnormalities in the right breast. Staging with a computed tomographic torso scan and bone scan revealed no distant sites of metastasis.
1526-8209/$ - see frontmatter © 2011 Elsevier Inc. All rights reserved. doi: 10.1016/j.clbc.2011.06.009
Figure 1 Left Breast Mammogram Shows Cluster Calcifications Within the Deep Central Breast
Figure 2 (A) Right Breast Mammogram, MLO View, Shows New Right Axillary Lesions Concerning for Malignant Nodal Involvement. The Breast Parenchyma Had no Concerning Lesions. (B) Right Breast Ultrasound Shows Two Hypoechoic Lesions in the Right Axilla
A
B
The patient opted for bilateral mastectomies and right ALND. Left-sided axillary dissection was not performed because of prior surgery to this area at the time of her previous breast cancer. Pathology demonstrated a left-sided 1.5-cm poorly differentiated invasive ductal carcinoma. IHC showed lack of expression for ER and low expression of progesterone receptor; HER-2 was not amplified by fluorescence in situ hybridization. One of 11 right-sided axillary lymph nodes showed metastatic adenocarcinoma in a 3-cm mass with extranodal extension. There was no carcinoma noted by pathologic examination of the right breast specimen. She was then treated with adjuvant chemotherapy, consisting of four cycles of docetaxel and cyclophosphamide, followed by right chest wall and low axilla tangential and bilateral high axilla and supraclavicular nodal irradiation. These fields were gapped medially and inferiorly to her previous left breast tangent fields, and treated with 180 cGy ⫻ 28 to 5040 cGy. Genetic testing for BRCA1, BRCA2, and p53 mutations were negative. Currently, at 24-month follow-up examination from the diagnosis of her second breast cancer, she remains free of recurrence without further breast cancer treatment.
Discussion In the setting of a new diagnosis of breast cancer, what is the clinical implication of contralateral axillary lymph node involvement? In the absence of other distant metastatic sites, should these patients be treated as having advanced breast cancer or should they be viewed as having early-stage disease with aberrant lymphatic drainage and therefore eligible for treatments with curative intent? In the present case report, our patient was considered to have a second
primary ipsilateral breast cancer, rather than a local recurrence, because of the length of time that had elapsed since her initial breast cancer and the differing locations of the first and second cancers. After extensive multi-disciplinary consultation, she was treated with curative intent and has remained free of recurrence to date. Previous surgical studies have investigated the frequency with which initial breast cancers drain to sites other than the ipsilateral axilla. In one study, 700 patients with clinically node-negative breast cancer underwent lymphatic mapping with preoperative lymphoscintigraphy followed by sentinel lymph node biopsy (SNB).1 These patients were analyzed by location of the primary breast tumor: upper outer quadrant, upper inner quadrant, lower outer quadrant, lower inner quadrant, and central. The overall sentinel lymph node non-identification rate was only 3.1%. Extra-axillary sentinel lymphatic drainage was found for tumors in all five locations. For the overall breast, the location and frequency of lymphatic drainage included: axillary (92.3%), internal mammary (21.1%), intramammary (7.1%), subclavicular (2.6%), interpectoral (2.1%), and supraclavicular (0.4%). In total, approximately 33% of patients exhibited lymphatic drainage patterns that included one or more extra-axillary lymph node basins.1,2 As expected, inner quadrant medial breast
Clinical Breast Cancer December 2011
407
Second Primary Breast Cancer With Contralateral Axillary Involvement cancers were more likely to show internal mammary lymph node drainage than outer quadrant lateral breast cancers (37.4% versus 14.4%, P ⬍ .001). Of particular interest to this case report, the same surgical group later conducted a similar study to investigate lymphatic drainage patterns in breast cancer patients who had undergone prior surgery of the ipsilateral breast.2 Of the 115 patients analyzed, 41% had also undergone surgery to the ipsilateral axilla: 31% had undergone prior BCS with SNB only, 10% had undergone prior BCS with ALND, 50% had undergone prior excisional biopsy only, and 9% had undergone prior breast reduction or augmentation. For the overall cohort, sentinel nodes were identified in only 84%; this 16% nonidentification rate was significantly higher than the 3.1% rate in patients who had not undergone prior surgery (P ⫽ .003).1,2 In addition, lymphatic drainage to lymph nodes outside of the ipsilateral axilla were more common in this cohort than in those who were not treated with breast surgery (51% versus 33%, P ⫽ .01). Notably, four patients (3.5%) showed contralateral axillary drainage whereas no patients in the initial breast cancer cohort showed this drainage pattern. Our case report is the second case of this type to be reported in the literature. Kinoshita et al reported a case of a patient with a second primary ipsilateral breast cancer who presented with contralateral axillary lymph node involvement.3 This patient was also treated with curative intent, including surgery and radiation, and remained free of disease recurrence at 36 months of follow-up. In both case reports, contralateral axillary lymph node involvement was clinically evident when the patient presented with a second primary ipsilateral breast cancer. However, a larger related issue is whether to pursue SNB in all women who present with a second primary ipsilateral breast cancer and who have undergone prior axillary surgery. In 2005 guidelines, the American Society of Clinical Oncology discouraged this practice citing limited evidence and cautioned that although SNB may be undertaken in this scenario, the success rate is likely to be low.4 In one small study, 15 patients with IBTR and prior BCS with SNB and/or ALND underwent preoperative lymphoscintigraphy before repeat SNB.5 Lymphatic drainage was identified in only 11 (73%) of the patients and 3 (20%) were found to have contralateral axillary drainage. Similarly, in a second study, sentinel node identification was successful in only 24 (75%) patients with second primary ipsilateral breast cancers or IBTR who had undergone prior axillary surgery.6
408
Clinical Breast Cancer December 2011
Conclusion The clinical challenge raised in this case report is whether to treat a patient with newly diagnosed breast cancer and concurrent contralateral axillary tumor involvement with curative intent. Although rare, the clinical issue raised is also relevant to the far more common scenario of IBTR. After BCS, the rate of IBTR at 10 years is estimated to be 10%.7 Our review found that after prior breast surgery and SNB or ALND, the incidence of lymphatic drainage to sites other than the ipsilateral axilla increases from 33%1,2 to 51%2 at the time of a second primary ipsilateral breast cancer. In addition, there are several reports of lymphatic drainage to contralateral axillary nodes.2,5 It is not known whether the lower prevalence of sentinel nodes identified after breast and axillary surgery is attributable to anatomic changes from the surgery or to lymph node drainage outside of the ipsilateral axilla.1,2,5,6 This clinical issue is likely to become more common as the incidence of second primary ipsilateral breast cancer and IBTR would both be expected to increase due to widespread adoption of BCS, improved prognosis for patients with an initial early-stage breast cancer, and highly sensitive screening modalities such as MRI. Therefore, we propose that careful consideration be given to viewing cases of second primary ipsilateral breast cancers or IBTR with contralateral axillary involvement as representing potentially curable disease with regional nodal involvement rather than distant metastatic extent.
Disclosure All authors have no conflicts of interest.
References 1. Estourgie SH, Nieweg OE, Valdés Olmes RA, et al. Lymphatic drainage patterns from the breast. Ann Surg 2004; 239:232-7. 2. van der Ploeg IMC, Oldenburg HSA, Rutgers EJT, et al. Lymphatic drainage patterns from the treated breast. Ann Surg Oncol 2010; 17:1069-75. 3. Kinoshita S, Hirano A, Kobayashi S, et al. Metachronous second primary occult breast cancer initially presenting with metastases to the contralateral axillary lymph nodes: report of a case. Breast Cancer 2010; 17:71-4. 4. Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 2005; 23:7703-20. 5. Taback B, Nguyen P, Hansen N, et al. Sentinel lymph node biopsy for local recurrence of breast cancer after breast-conserving therapy. Ann Surg Onc 2006; 13:1099-104. 6. Port ER, Fey J, Gemignani ML, et al. Reoperative sentinel lymph node biopsy: a new option for patients with primary or locally recurrent breast carcinoma. J Am Coll Surg 2002; 195:167-72. 7. Fisher B, Anderson S, Redmond CK, et al. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1995; 333:1456-61.
Second Primary Ipsilateral Breast Cancer With Contralateral Axillary Involvement: A Case Report and Literature Review Christina I. Herold,1 Elizabeth M. Gaughan,1 Carolyn C. Lamb,2 Nadine M. Tung1 Clinical Practice Points ●
●
After breast-conserving surgery for an initial breast cancer, the incidence of lymphatic drainage to sites other than the ipsilateral axilla, such as the contralateral axilla, increases significantly at the time of a second primary ipsilateral breast cancer. Given the likelihood of altered lymphatic drainage, and in the absence of distant metastatic sites, consideration should be given to treating patients with a second primary ipsilateral breast cancer and con-
●
tralateral axillary lymph node involvement with curative intent. This clinical issue may become more common as the incidence of second primary ipsilateral breast cancer would be expected to increase due to widespread adoption of breast-conserving surgery, improved prognosis for patients with an initial early-stage breast cancer, and highly sensitive screening modalities such as magnetic resonance imaging.
Clinical Breast Cancer, Vol. 11, No. 6, 406-8 © 2011 Elsevier Inc. All rights reserved. Keywords: Ipsilateral breast tumor recurrence, Second primary ipsilateral breast cancer, Sentinel lymph node biopsy
Introduction The significance of contralateral axillary tumor involvement at the time of a new breast cancer diagnosis is not clear. Whether to treat such patients with curative intent, if staging workup for distant metastatic disease is negative, is not known. We report a case of a woman with a second primary ipsilateral breast cancer who presented with contralateral lymph node involvement. The literature evaluating lymphatic drainage of breast cancers to sites other than the ipsilateral axilla is reviewed. Particular attention is paid to whether such drainage is altered by previous breast and/or axillary surgery in the setting of either a new ipsilateral breast primary or ipsilateral breast tumor recurrence (IBTR).
Case Report In 2000, at the age of 22 years, the patient presented with a palpable lesion in the axillary tail of her left breast. She underwent left breast-conserving surgery (BCS) and axillary lymph node dissection 1 Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 2 Division of Radiation Oncology, Mt. Auburn Hospital, Cambridge, MA
Submitted: Jun 23, 2011; Accepted: Jun 27, 2011 Address for correspondence: Christina I. Herold, MD, Beth Israel Deaconess Medical Center, 330 Brookline Ave, KS-108C, Boston, MA 02215 Tel: 617-667-1970; Fax: 617-667-1960; e-mail contact: [email protected]
406
Clinical Breast Cancer December 2011
(ALND). Pathology showed a 1.5-cm poorly differentiated invasive ductal carcinoma that was estrogen receptor (ER)-negative and lacked over-expression of human epidermal growth factor receptor 2 (HER-2) by immunohistochemistry (IHC); 11 lymph nodes showed no evidence of metastatic disease. In the adjuvant setting she was treated with four cycles of doxorubicin and cyclophosphamide followed by radiation therapy to the whole breast (180 cGy ⫻ 25) and a boost to the axillary tail tumor bed for an additional 16 Gy. She was subsequently followed-up every 6 months with clinical examinations as well as breast surveillance with alternating mammography and magnetic resonance imaging (MRI) of the breast. In 2009, at the age of 31 years, interval screening mammography revealed new calcifications in the deep medial aspect of the patient’s left breast (Figure 1). Core biopsy was diagnostic of invasive ductal carcinoma. This tumor was believed to represent a second primary breast cancer of the left breast because it was located in a different quadrant and occurred 9 years from the initial cancer. The patient subsequently reported contralateral right axillary pain and fullness which was confirmed by physical examination and breast imaging (Figure 2). Fine-needle aspiration of an enlarged right axillary node confirmed metastatic carcinoma. Right breast imaging was significant only for malignant axillary lymphadenopathy; there were no other abnormalities in the right breast. Staging with a computed tomographic torso scan and bone scan revealed no distant sites of metastasis.
1526-8209/$ - see frontmatter © 2011 Elsevier Inc. All rights reserved. doi: 10.1016/j.clbc.2011.06.009
Figure 1 Left Breast Mammogram Shows Cluster Calcifications Within the Deep Central Breast
Figure 2 (A) Right Breast Mammogram, MLO View, Shows New Right Axillary Lesions Concerning for Malignant Nodal Involvement. The Breast Parenchyma Had no Concerning Lesions. (B) Right Breast Ultrasound Shows Two Hypoechoic Lesions in the Right Axilla
A
B
The patient opted for bilateral mastectomies and right ALND. Left-sided axillary dissection was not performed because of prior surgery to this area at the time of her previous breast cancer. Pathology demonstrated a left-sided 1.5-cm poorly differentiated invasive ductal carcinoma. IHC showed lack of expression for ER and low expression of progesterone receptor; HER-2 was not amplified by fluorescence in situ hybridization. One of 11 right-sided axillary lymph nodes showed metastatic adenocarcinoma in a 3-cm mass with extranodal extension. There was no carcinoma noted by pathologic examination of the right breast specimen. She was then treated with adjuvant chemotherapy, consisting of four cycles of docetaxel and cyclophosphamide, followed by right chest wall and low axilla tangential and bilateral high axilla and supraclavicular nodal irradiation. These fields were gapped medially and inferiorly to her previous left breast tangent fields, and treated with 180 cGy ⫻ 28 to 5040 cGy. Genetic testing for BRCA1, BRCA2, and p53 mutations were negative. Currently, at 24-month follow-up examination from the diagnosis of her second breast cancer, she remains free of recurrence without further breast cancer treatment.
Discussion In the setting of a new diagnosis of breast cancer, what is the clinical implication of contralateral axillary lymph node involvement? In the absence of other distant metastatic sites, should these patients be treated as having advanced breast cancer or should they be viewed as having early-stage disease with aberrant lymphatic drainage and therefore eligible for treatments with curative intent? In the present case report, our patient was considered to have a second
primary ipsilateral breast cancer, rather than a local recurrence, because of the length of time that had elapsed since her initial breast cancer and the differing locations of the first and second cancers. After extensive multi-disciplinary consultation, she was treated with curative intent and has remained free of recurrence to date. Previous surgical studies have investigated the frequency with which initial breast cancers drain to sites other than the ipsilateral axilla. In one study, 700 patients with clinically node-negative breast cancer underwent lymphatic mapping with preoperative lymphoscintigraphy followed by sentinel lymph node biopsy (SNB).1 These patients were analyzed by location of the primary breast tumor: upper outer quadrant, upper inner quadrant, lower outer quadrant, lower inner quadrant, and central. The overall sentinel lymph node non-identification rate was only 3.1%. Extra-axillary sentinel lymphatic drainage was found for tumors in all five locations. For the overall breast, the location and frequency of lymphatic drainage included: axillary (92.3%), internal mammary (21.1%), intramammary (7.1%), subclavicular (2.6%), interpectoral (2.1%), and supraclavicular (0.4%). In total, approximately 33% of patients exhibited lymphatic drainage patterns that included one or more extra-axillary lymph node basins.1,2 As expected, inner quadrant medial breast
Clinical Breast Cancer December 2011
407
Second Primary Breast Cancer With Contralateral Axillary Involvement cancers were more likely to show internal mammary lymph node drainage than outer quadrant lateral breast cancers (37.4% versus 14.4%, P ⬍ .001). Of particular interest to this case report, the same surgical group later conducted a similar study to investigate lymphatic drainage patterns in breast cancer patients who had undergone prior surgery of the ipsilateral breast.2 Of the 115 patients analyzed, 41% had also undergone surgery to the ipsilateral axilla: 31% had undergone prior BCS with SNB only, 10% had undergone prior BCS with ALND, 50% had undergone prior excisional biopsy only, and 9% had undergone prior breast reduction or augmentation. For the overall cohort, sentinel nodes were identified in only 84%; this 16% nonidentification rate was significantly higher than the 3.1% rate in patients who had not undergone prior surgery (P ⫽ .003).1,2 In addition, lymphatic drainage to lymph nodes outside of the ipsilateral axilla were more common in this cohort than in those who were not treated with breast surgery (51% versus 33%, P ⫽ .01). Notably, four patients (3.5%) showed contralateral axillary drainage whereas no patients in the initial breast cancer cohort showed this drainage pattern. Our case report is the second case of this type to be reported in the literature. Kinoshita et al reported a case of a patient with a second primary ipsilateral breast cancer who presented with contralateral axillary lymph node involvement.3 This patient was also treated with curative intent, including surgery and radiation, and remained free of disease recurrence at 36 months of follow-up. In both case reports, contralateral axillary lymph node involvement was clinically evident when the patient presented with a second primary ipsilateral breast cancer. However, a larger related issue is whether to pursue SNB in all women who present with a second primary ipsilateral breast cancer and who have undergone prior axillary surgery. In 2005 guidelines, the American Society of Clinical Oncology discouraged this practice citing limited evidence and cautioned that although SNB may be undertaken in this scenario, the success rate is likely to be low.4 In one small study, 15 patients with IBTR and prior BCS with SNB and/or ALND underwent preoperative lymphoscintigraphy before repeat SNB.5 Lymphatic drainage was identified in only 11 (73%) of the patients and 3 (20%) were found to have contralateral axillary drainage. Similarly, in a second study, sentinel node identification was successful in only 24 (75%) patients with second primary ipsilateral breast cancers or IBTR who had undergone prior axillary surgery.6
408
Clinical Breast Cancer December 2011
Conclusion The clinical challenge raised in this case report is whether to treat a patient with newly diagnosed breast cancer and concurrent contralateral axillary tumor involvement with curative intent. Although rare, the clinical issue raised is also relevant to the far more common scenario of IBTR. After BCS, the rate of IBTR at 10 years is estimated to be 10%.7 Our review found that after prior breast surgery and SNB or ALND, the incidence of lymphatic drainage to sites other than the ipsilateral axilla increases from 33%1,2 to 51%2 at the time of a second primary ipsilateral breast cancer. In addition, there are several reports of lymphatic drainage to contralateral axillary nodes.2,5 It is not known whether the lower prevalence of sentinel nodes identified after breast and axillary surgery is attributable to anatomic changes from the surgery or to lymph node drainage outside of the ipsilateral axilla.1,2,5,6 This clinical issue is likely to become more common as the incidence of second primary ipsilateral breast cancer and IBTR would both be expected to increase due to widespread adoption of BCS, improved prognosis for patients with an initial early-stage breast cancer, and highly sensitive screening modalities such as MRI. Therefore, we propose that careful consideration be given to viewing cases of second primary ipsilateral breast cancers or IBTR with contralateral axillary involvement as representing potentially curable disease with regional nodal involvement rather than distant metastatic extent.
Disclosure All authors have no conflicts of interest.
References 1. Estourgie SH, Nieweg OE, Valdés Olmes RA, et al. Lymphatic drainage patterns from the breast. Ann Surg 2004; 239:232-7. 2. van der Ploeg IMC, Oldenburg HSA, Rutgers EJT, et al. Lymphatic drainage patterns from the treated breast. Ann Surg Oncol 2010; 17:1069-75. 3. Kinoshita S, Hirano A, Kobayashi S, et al. Metachronous second primary occult breast cancer initially presenting with metastases to the contralateral axillary lymph nodes: report of a case. Breast Cancer 2010; 17:71-4. 4. Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 2005; 23:7703-20. 5. Taback B, Nguyen P, Hansen N, et al. Sentinel lymph node biopsy for local recurrence of breast cancer after breast-conserving therapy. Ann Surg Onc 2006; 13:1099-104. 6. Port ER, Fey J, Gemignani ML, et al. Reoperative sentinel lymph node biopsy: a new option for patients with primary or locally recurrent breast carcinoma. J Am Coll Surg 2002; 195:167-72. 7. Fisher B, Anderson S, Redmond CK, et al. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1995; 333:1456-61.