Advanced Breast Cancer

The history and findings in this case are suggestive of advanced/metastatic breast cancer. 

Breast cancer is the most frequently diagnosed life-threatening cancer and the second-leading cause of cancer-related deaths in women worldwide. In the United States, an estimated 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 women died of the disease. Globally, approximately 2.3 million new diagnoses and 685,000 breast cancer–related deaths were reported in 2020.

Tumor size, nodal spread, and distant metastases (TNM) at the time of diagnosis are key prognostic factors. Immunohistochemistry tumor markers (ie, estrogen receptor [ER], progesterone receptor [PR], and HER2), as well as grade and Ki-67 expression, have also been shown to be independent predictors of breast cancer death and are used together with TNM to guide treatment decisions. 

Despite advances in breast cancer diagnosis and treatment, metastatic recurrence remains a significant problem. Although the incidence of distance relapse is declining and survival times for patients with recurrent disease are improving, 20%-30% of patients with early breast cancer still die of metastatic disease. Metastatic breast cancer recurrence can arise months to decades after initial diagnosis and treatment. 

According to the National Comprehensive Cancer Network (NCCN) guidelines, biopsy is a critical component of the workup for patients with recurrent or stage IV disease. This is because biopsy ensures accurate determination of metastatic/recurrent disease and tumor histology and enables biomarker determination and selection of appropriate treatment. Soft-tissue tumor biopsy is preferred over bone sites unless a portion of the biopsy can be protected from harsh decalcification solution to preserve more accurate evaluation of biomarkers. Determination of HR status (ER and PR) and HER2 status should be repeated in all cases when diagnostic tissue is obtained because ER and PR assays may be falsely negative or falsely positive, and there may be discordance between the primary and metastatic tumors. According to the NCCN panel, re-testing the receptor status of recurrent disease should be performed, particularly when it was previously unknown, originally negative, or not overexpressed. 

Additionally, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include history and physical exam; a complete blood cell count, liver function tests, chest diagnostic CT, bone scan, and radiography of any long or weight-bearing bones that are painful or appear abnormal on bone scan; diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen; and biopsy documentation of first recurrence whenever possible. The use of sodium fluoride PET or PET/CT for evaluating patients with recurrent disease is generally discouraged. 

Presently, metastatic breast cancer remains incurable. However, in recent years, the treatment landscape for metastatic breast cancer has significantly advanced in all breast cancer subtypes, leading to improvements in progression-free survival and even overall survival in some cases. For example, newer, targeted approaches directly address mutation drivers and allow precise delivery of chemotherapeutic agents. Detailed guidance on the treatment of breast cancer can be found here and in the full NCCN guidelines. 

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of advanced/metastatic breast cancer. 

Breast cancer is the most frequently diagnosed life-threatening cancer and the second-leading cause of cancer-related deaths in women worldwide. In the United States, an estimated 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 women died of the disease. Globally, approximately 2.3 million new diagnoses and 685,000 breast cancer–related deaths were reported in 2020.

Tumor size, nodal spread, and distant metastases (TNM) at the time of diagnosis are key prognostic factors. Immunohistochemistry tumor markers (ie, estrogen receptor [ER], progesterone receptor [PR], and HER2), as well as grade and Ki-67 expression, have also been shown to be independent predictors of breast cancer death and are used together with TNM to guide treatment decisions. 

Despite advances in breast cancer diagnosis and treatment, metastatic recurrence remains a significant problem. Although the incidence of distance relapse is declining and survival times for patients with recurrent disease are improving, 20%-30% of patients with early breast cancer still die of metastatic disease. Metastatic breast cancer recurrence can arise months to decades after initial diagnosis and treatment. 

According to the National Comprehensive Cancer Network (NCCN) guidelines, biopsy is a critical component of the workup for patients with recurrent or stage IV disease. This is because biopsy ensures accurate determination of metastatic/recurrent disease and tumor histology and enables biomarker determination and selection of appropriate treatment. Soft-tissue tumor biopsy is preferred over bone sites unless a portion of the biopsy can be protected from harsh decalcification solution to preserve more accurate evaluation of biomarkers. Determination of HR status (ER and PR) and HER2 status should be repeated in all cases when diagnostic tissue is obtained because ER and PR assays may be falsely negative or falsely positive, and there may be discordance between the primary and metastatic tumors. According to the NCCN panel, re-testing the receptor status of recurrent disease should be performed, particularly when it was previously unknown, originally negative, or not overexpressed. 

Additionally, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include history and physical exam; a complete blood cell count, liver function tests, chest diagnostic CT, bone scan, and radiography of any long or weight-bearing bones that are painful or appear abnormal on bone scan; diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen; and biopsy documentation of first recurrence whenever possible. The use of sodium fluoride PET or PET/CT for evaluating patients with recurrent disease is generally discouraged. 

Presently, metastatic breast cancer remains incurable. However, in recent years, the treatment landscape for metastatic breast cancer has significantly advanced in all breast cancer subtypes, leading to improvements in progression-free survival and even overall survival in some cases. For example, newer, targeted approaches directly address mutation drivers and allow precise delivery of chemotherapeutic agents. Detailed guidance on the treatment of breast cancer can be found here and in the full NCCN guidelines. 

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of advanced/metastatic breast cancer. 

Breast cancer is the most frequently diagnosed life-threatening cancer and the second-leading cause of cancer-related deaths in women worldwide. In the United States, an estimated 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 women died of the disease. Globally, approximately 2.3 million new diagnoses and 685,000 breast cancer–related deaths were reported in 2020.

Tumor size, nodal spread, and distant metastases (TNM) at the time of diagnosis are key prognostic factors. Immunohistochemistry tumor markers (ie, estrogen receptor [ER], progesterone receptor [PR], and HER2), as well as grade and Ki-67 expression, have also been shown to be independent predictors of breast cancer death and are used together with TNM to guide treatment decisions. 

Despite advances in breast cancer diagnosis and treatment, metastatic recurrence remains a significant problem. Although the incidence of distance relapse is declining and survival times for patients with recurrent disease are improving, 20%-30% of patients with early breast cancer still die of metastatic disease. Metastatic breast cancer recurrence can arise months to decades after initial diagnosis and treatment. 

According to the National Comprehensive Cancer Network (NCCN) guidelines, biopsy is a critical component of the workup for patients with recurrent or stage IV disease. This is because biopsy ensures accurate determination of metastatic/recurrent disease and tumor histology and enables biomarker determination and selection of appropriate treatment. Soft-tissue tumor biopsy is preferred over bone sites unless a portion of the biopsy can be protected from harsh decalcification solution to preserve more accurate evaluation of biomarkers. Determination of HR status (ER and PR) and HER2 status should be repeated in all cases when diagnostic tissue is obtained because ER and PR assays may be falsely negative or falsely positive, and there may be discordance between the primary and metastatic tumors. According to the NCCN panel, re-testing the receptor status of recurrent disease should be performed, particularly when it was previously unknown, originally negative, or not overexpressed. 

Additionally, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include history and physical exam; a complete blood cell count, liver function tests, chest diagnostic CT, bone scan, and radiography of any long or weight-bearing bones that are painful or appear abnormal on bone scan; diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen; and biopsy documentation of first recurrence whenever possible. The use of sodium fluoride PET or PET/CT for evaluating patients with recurrent disease is generally discouraged. 

Presently, metastatic breast cancer remains incurable. However, in recent years, the treatment landscape for metastatic breast cancer has significantly advanced in all breast cancer subtypes, leading to improvements in progression-free survival and even overall survival in some cases. For example, newer, targeted approaches directly address mutation drivers and allow precise delivery of chemotherapeutic agents. Detailed guidance on the treatment of breast cancer can be found here and in the full NCCN guidelines. 

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are consistent with advanced infiltrating ductal carcinoma. 

Breast cancer is the most commonly diagnosed life-threatening cancer and the leading cause of cancer death among women worldwide. In the United States, it is estimated that 287,850 new cases of invasive breast cancer were diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. 

Infiltrating ductal carcinoma is the most common type of breast tumor. It accounts for 75% of breast cancers and has a propensity to metastasize via lymphatic vessels. This lesion has no specific histologic characteristics apart from invasion through the basement membrane. This enables it to be differentiated from ductal carcinoma in situ, which remains inside the duct. 

All newly diagnosed cases of invasive breast cancers are tested for estrogen receptors, progesterone receptors, and HER2 status. The presence of estrogen and progesterone receptors is tested by immunohistochemistry, whereas HER2 can be tested by either immunohistochemistry or in situ hybridization (usually fluorescent or fluorescence in situ hybridization). Testing results have important treatment implications and prognostic significance. 

Surgical treatment of invasive breast cancer consists of either lumpectomy or total mastectomy, followed by radiation therapy. Surgical resection is performed in all patients with nonmetastatic disease. 

Systemic therapy options include endocrine therapy, cytotoxic chemotherapy, targeted therapy, and immunotherapy. The choice of systemic therapy is largely determined by subtype. For example, patients with hormone receptor–positive tumors receive endocrine therapy; a minority of these patients may receive chemotherapy as well. Patients with HER2-positive tumors receive HER2–targeted antibody or small-molecule inhibitor therapy combined with chemotherapy. For patients with triple-negative tumors, chemotherapy alone is often used; newer targeted therapies however may improve outcomes. In both the adjuvant and neoadjuvant setting, the primary goal of treatment is to eradicate or control undiscovered distant metastases. In the metastatic setting, the primary goal of treatment is to extend life and alleviate symptoms. 

Depending on the individual patient, systemic therapy may be used in the adjuvant or neoadjuvant setting. Systemic therapy is chosen according to breast cancer subtype and recurrence risk, with the treatment for low-risk patients being de-escalated, whereas high-risk patients receive aggressive systemic treatment. When systemic therapy is used in the neoadjuvant setting, treatment response is the most important factor for predicting outcomes and selecting the optimal adjuvant therapy. Novel biological markers enable the selection of appropriate targeted therapy, which can achieve optimal efficacy. 

Up-to-date, evidence-based recommendations for pre- and postoperative treatment of breast cancer, including advanced breast cancer, are provided by the National Comprehensive Cancer Network.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are consistent with advanced infiltrating ductal carcinoma. 

Breast cancer is the most commonly diagnosed life-threatening cancer and the leading cause of cancer death among women worldwide. In the United States, it is estimated that 287,850 new cases of invasive breast cancer were diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. 

Infiltrating ductal carcinoma is the most common type of breast tumor. It accounts for 75% of breast cancers and has a propensity to metastasize via lymphatic vessels. This lesion has no specific histologic characteristics apart from invasion through the basement membrane. This enables it to be differentiated from ductal carcinoma in situ, which remains inside the duct. 

All newly diagnosed cases of invasive breast cancers are tested for estrogen receptors, progesterone receptors, and HER2 status. The presence of estrogen and progesterone receptors is tested by immunohistochemistry, whereas HER2 can be tested by either immunohistochemistry or in situ hybridization (usually fluorescent or fluorescence in situ hybridization). Testing results have important treatment implications and prognostic significance. 

Surgical treatment of invasive breast cancer consists of either lumpectomy or total mastectomy, followed by radiation therapy. Surgical resection is performed in all patients with nonmetastatic disease. 

Systemic therapy options include endocrine therapy, cytotoxic chemotherapy, targeted therapy, and immunotherapy. The choice of systemic therapy is largely determined by subtype. For example, patients with hormone receptor–positive tumors receive endocrine therapy; a minority of these patients may receive chemotherapy as well. Patients with HER2-positive tumors receive HER2–targeted antibody or small-molecule inhibitor therapy combined with chemotherapy. For patients with triple-negative tumors, chemotherapy alone is often used; newer targeted therapies however may improve outcomes. In both the adjuvant and neoadjuvant setting, the primary goal of treatment is to eradicate or control undiscovered distant metastases. In the metastatic setting, the primary goal of treatment is to extend life and alleviate symptoms. 

Depending on the individual patient, systemic therapy may be used in the adjuvant or neoadjuvant setting. Systemic therapy is chosen according to breast cancer subtype and recurrence risk, with the treatment for low-risk patients being de-escalated, whereas high-risk patients receive aggressive systemic treatment. When systemic therapy is used in the neoadjuvant setting, treatment response is the most important factor for predicting outcomes and selecting the optimal adjuvant therapy. Novel biological markers enable the selection of appropriate targeted therapy, which can achieve optimal efficacy. 

Up-to-date, evidence-based recommendations for pre- and postoperative treatment of breast cancer, including advanced breast cancer, are provided by the National Comprehensive Cancer Network.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are consistent with advanced infiltrating ductal carcinoma. 

Breast cancer is the most commonly diagnosed life-threatening cancer and the leading cause of cancer death among women worldwide. In the United States, it is estimated that 287,850 new cases of invasive breast cancer were diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. 

Infiltrating ductal carcinoma is the most common type of breast tumor. It accounts for 75% of breast cancers and has a propensity to metastasize via lymphatic vessels. This lesion has no specific histologic characteristics apart from invasion through the basement membrane. This enables it to be differentiated from ductal carcinoma in situ, which remains inside the duct. 

All newly diagnosed cases of invasive breast cancers are tested for estrogen receptors, progesterone receptors, and HER2 status. The presence of estrogen and progesterone receptors is tested by immunohistochemistry, whereas HER2 can be tested by either immunohistochemistry or in situ hybridization (usually fluorescent or fluorescence in situ hybridization). Testing results have important treatment implications and prognostic significance. 

Surgical treatment of invasive breast cancer consists of either lumpectomy or total mastectomy, followed by radiation therapy. Surgical resection is performed in all patients with nonmetastatic disease. 

Systemic therapy options include endocrine therapy, cytotoxic chemotherapy, targeted therapy, and immunotherapy. The choice of systemic therapy is largely determined by subtype. For example, patients with hormone receptor–positive tumors receive endocrine therapy; a minority of these patients may receive chemotherapy as well. Patients with HER2-positive tumors receive HER2–targeted antibody or small-molecule inhibitor therapy combined with chemotherapy. For patients with triple-negative tumors, chemotherapy alone is often used; newer targeted therapies however may improve outcomes. In both the adjuvant and neoadjuvant setting, the primary goal of treatment is to eradicate or control undiscovered distant metastases. In the metastatic setting, the primary goal of treatment is to extend life and alleviate symptoms. 

Depending on the individual patient, systemic therapy may be used in the adjuvant or neoadjuvant setting. Systemic therapy is chosen according to breast cancer subtype and recurrence risk, with the treatment for low-risk patients being de-escalated, whereas high-risk patients receive aggressive systemic treatment. When systemic therapy is used in the neoadjuvant setting, treatment response is the most important factor for predicting outcomes and selecting the optimal adjuvant therapy. Novel biological markers enable the selection of appropriate targeted therapy, which can achieve optimal efficacy. 

Up-to-date, evidence-based recommendations for pre- and postoperative treatment of breast cancer, including advanced breast cancer, are provided by the National Comprehensive Cancer Network.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's clinical presentation is consistent with a diagnosis of metastatic invasive lobular carcinoma, with nodal involvement. 

Breast cancer is one of the most frequently diagnosed cancers worldwide. In Western countries, 1 in 8 women will be diagnosed with breast cancer at some point in their lives. Various histologic subtypes with specific clinical characteristics exist. Invasive lobular carcinoma (ILC) is the second most common subtype, accounting for an estimated 10%-15% of breast cancers. Over the past two decades, a significant increase has been observed in the incidence of ILC, particularly among postmenopausal women. Improved diagnostic techniques and the use of hormone replacement therapy may account for this increased incidence. White women have the highest incidence of ILC; however, compared with White women and women of other races, Black women experience the worst 5-year overall survival from ILC.

ILC arises in the mammary ducts (lobules) of the breast. Women with ILC are typically slightly older than women with invasive breast cancer of no special type at diagnosis (mean age 63.4 vs 59.5 years, respectively). Risk factors for ILC may include early menarche, use of progesterone-based hormone replacement therapy, late age at first live birth, and alcohol consumption. 

In most cases, ILC does not form a discrete palpable mass until it has reached an advanced stage, making it more difficult to detect through physical examination or imaging. Patients often present with a large tumor and with nodal involvement. A slight thickening of the nipple, an exudative scab on the skin, or other changes in the skin, such as flushing or swelling, may be seen in patients presenting with advanced disease. Additionally, ILC tumors are often bilateral and multifocal. 

ILC is predominantly a histopathologic diagnosis based on standard hematoxylin and eosin staining. Histologically, ILC is characterized by a proliferation of small cells that lack cohesion. These cells are often dispersed individually through a fibrous connective tissue; alternatively, they may be organized in single-file linear cords invading the stroma. A concentric pattern around normal ducts is often seen in the infiltrating cords. There is usually little host reaction of the background architecture. Round or notched ovoid nuclei are seen in the neoplastic cells, along with a thin rim of cytoplasm. Occasionally, an intracytoplasmic lumen is present and may harbor a central mucoid inclusion. Very few or no mitoses are seen.

Several variants of ILC exist, all of which lack cell-to-cell cohesion. These include:

•    Solid type
•    Pleomorphic lobular carcinoma
•    Tubulo-lobular variant
•    Alveolar variant
•    Mixed type

Complete loss of E-cadherin expression occurs in most ILCs, which can help to differentiate it from invasive ductal cancers or ductal carcinomas in situ. Diffuse cortical thickening without hilar mass effect is often seen in nodal metastases associated with ILC. 

Most classic ILCs are estrogen receptor– and progesterone receptor–positive. Conversely, HER2 overexpression and amplification rarely occurs in ILC. 

Late relapses more than 10 years after remission may occur. In addition to frequent bone and liver metastasis, ILC is associated with metastatic spread to unusual sites, including the peritoneum, gastrointestinal tract, urinary tract, leptomeninges, skin, orbit, and ovaries. 

Mastectomy is often indicated in ILC. In the neoadjuvant setting, ILC is associated with low pathologic complete response rates. Endocrine therapy in the neoadjuvant setting is an emerging approach for some patients with ILC. According to 2022 National Comprehensive Cancer Network guidelines, adjuvant chemotherapy followed by endocrine therapy or endocrine therapy alone should be considered for pre- and postmenopausal patients with ILC.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.
 
Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's clinical presentation is consistent with a diagnosis of metastatic invasive lobular carcinoma, with nodal involvement. 

Breast cancer is one of the most frequently diagnosed cancers worldwide. In Western countries, 1 in 8 women will be diagnosed with breast cancer at some point in their lives. Various histologic subtypes with specific clinical characteristics exist. Invasive lobular carcinoma (ILC) is the second most common subtype, accounting for an estimated 10%-15% of breast cancers. Over the past two decades, a significant increase has been observed in the incidence of ILC, particularly among postmenopausal women. Improved diagnostic techniques and the use of hormone replacement therapy may account for this increased incidence. White women have the highest incidence of ILC; however, compared with White women and women of other races, Black women experience the worst 5-year overall survival from ILC.

ILC arises in the mammary ducts (lobules) of the breast. Women with ILC are typically slightly older than women with invasive breast cancer of no special type at diagnosis (mean age 63.4 vs 59.5 years, respectively). Risk factors for ILC may include early menarche, use of progesterone-based hormone replacement therapy, late age at first live birth, and alcohol consumption. 

In most cases, ILC does not form a discrete palpable mass until it has reached an advanced stage, making it more difficult to detect through physical examination or imaging. Patients often present with a large tumor and with nodal involvement. A slight thickening of the nipple, an exudative scab on the skin, or other changes in the skin, such as flushing or swelling, may be seen in patients presenting with advanced disease. Additionally, ILC tumors are often bilateral and multifocal. 

ILC is predominantly a histopathologic diagnosis based on standard hematoxylin and eosin staining. Histologically, ILC is characterized by a proliferation of small cells that lack cohesion. These cells are often dispersed individually through a fibrous connective tissue; alternatively, they may be organized in single-file linear cords invading the stroma. A concentric pattern around normal ducts is often seen in the infiltrating cords. There is usually little host reaction of the background architecture. Round or notched ovoid nuclei are seen in the neoplastic cells, along with a thin rim of cytoplasm. Occasionally, an intracytoplasmic lumen is present and may harbor a central mucoid inclusion. Very few or no mitoses are seen.

Several variants of ILC exist, all of which lack cell-to-cell cohesion. These include:

•    Solid type
•    Pleomorphic lobular carcinoma
•    Tubulo-lobular variant
•    Alveolar variant
•    Mixed type

Complete loss of E-cadherin expression occurs in most ILCs, which can help to differentiate it from invasive ductal cancers or ductal carcinomas in situ. Diffuse cortical thickening without hilar mass effect is often seen in nodal metastases associated with ILC. 

Most classic ILCs are estrogen receptor– and progesterone receptor–positive. Conversely, HER2 overexpression and amplification rarely occurs in ILC. 

Late relapses more than 10 years after remission may occur. In addition to frequent bone and liver metastasis, ILC is associated with metastatic spread to unusual sites, including the peritoneum, gastrointestinal tract, urinary tract, leptomeninges, skin, orbit, and ovaries. 

Mastectomy is often indicated in ILC. In the neoadjuvant setting, ILC is associated with low pathologic complete response rates. Endocrine therapy in the neoadjuvant setting is an emerging approach for some patients with ILC. According to 2022 National Comprehensive Cancer Network guidelines, adjuvant chemotherapy followed by endocrine therapy or endocrine therapy alone should be considered for pre- and postmenopausal patients with ILC.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.
 
Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's clinical presentation is consistent with a diagnosis of metastatic invasive lobular carcinoma, with nodal involvement. 

Breast cancer is one of the most frequently diagnosed cancers worldwide. In Western countries, 1 in 8 women will be diagnosed with breast cancer at some point in their lives. Various histologic subtypes with specific clinical characteristics exist. Invasive lobular carcinoma (ILC) is the second most common subtype, accounting for an estimated 10%-15% of breast cancers. Over the past two decades, a significant increase has been observed in the incidence of ILC, particularly among postmenopausal women. Improved diagnostic techniques and the use of hormone replacement therapy may account for this increased incidence. White women have the highest incidence of ILC; however, compared with White women and women of other races, Black women experience the worst 5-year overall survival from ILC.

ILC arises in the mammary ducts (lobules) of the breast. Women with ILC are typically slightly older than women with invasive breast cancer of no special type at diagnosis (mean age 63.4 vs 59.5 years, respectively). Risk factors for ILC may include early menarche, use of progesterone-based hormone replacement therapy, late age at first live birth, and alcohol consumption. 

In most cases, ILC does not form a discrete palpable mass until it has reached an advanced stage, making it more difficult to detect through physical examination or imaging. Patients often present with a large tumor and with nodal involvement. A slight thickening of the nipple, an exudative scab on the skin, or other changes in the skin, such as flushing or swelling, may be seen in patients presenting with advanced disease. Additionally, ILC tumors are often bilateral and multifocal. 

ILC is predominantly a histopathologic diagnosis based on standard hematoxylin and eosin staining. Histologically, ILC is characterized by a proliferation of small cells that lack cohesion. These cells are often dispersed individually through a fibrous connective tissue; alternatively, they may be organized in single-file linear cords invading the stroma. A concentric pattern around normal ducts is often seen in the infiltrating cords. There is usually little host reaction of the background architecture. Round or notched ovoid nuclei are seen in the neoplastic cells, along with a thin rim of cytoplasm. Occasionally, an intracytoplasmic lumen is present and may harbor a central mucoid inclusion. Very few or no mitoses are seen.

Several variants of ILC exist, all of which lack cell-to-cell cohesion. These include:

•    Solid type
•    Pleomorphic lobular carcinoma
•    Tubulo-lobular variant
•    Alveolar variant
•    Mixed type

Complete loss of E-cadherin expression occurs in most ILCs, which can help to differentiate it from invasive ductal cancers or ductal carcinomas in situ. Diffuse cortical thickening without hilar mass effect is often seen in nodal metastases associated with ILC. 

Most classic ILCs are estrogen receptor– and progesterone receptor–positive. Conversely, HER2 overexpression and amplification rarely occurs in ILC. 

Late relapses more than 10 years after remission may occur. In addition to frequent bone and liver metastasis, ILC is associated with metastatic spread to unusual sites, including the peritoneum, gastrointestinal tract, urinary tract, leptomeninges, skin, orbit, and ovaries. 

Mastectomy is often indicated in ILC. In the neoadjuvant setting, ILC is associated with low pathologic complete response rates. Endocrine therapy in the neoadjuvant setting is an emerging approach for some patients with ILC. According to 2022 National Comprehensive Cancer Network guidelines, adjuvant chemotherapy followed by endocrine therapy or endocrine therapy alone should be considered for pre- and postmenopausal patients with ILC.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.
 
Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.