ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

The role of local therapies in metastatic breast cancer

The role of local therapies in metastatic breast cancer
Literature review current through: Jan 2024.
This topic last updated: Jan 05, 2024.

INTRODUCTION — Stage IV breast cancer, either de novo at presentation or secondary after a primary diagnosis, is a heterogeneous disease. While patients with metastatic breast cancer are unlikely to be cured of their disease, more effective systemic therapies with chemotherapy and targeted endocrine and biologic therapies have contributed to significantly improved overall survival and progression-free survival in the past decade, particularly among those with hormone receptor-positive and/or human epidermal growth factor receptor 2 (HER2)-positive disease [1-4]. The median survival for patients with stage IV breast cancer is now 18 to 36 months, although the range extends from a few months to many years and may vary widely by patient, tumor, and treatment factors including age, performance status, comorbidities, extent and location of distant disease, biologic subtype, and availability of effective systemic therapy [1-5]. (See "Overview of the approach to metastatic breast cancer" and "Tumor, node, metastasis (TNM) staging classification for breast cancer".)

Although systemic therapy is the mainstay of treatment for metastatic breast cancer, local management of both of the primary breast cancer, as well as metastasis-specific local treatment (ie, metastasectomy, radiation therapy, radiofrequency ablation, cryotherapy, and other image-guided percutaneous interventional procedures) may palliate symptoms and prevent cancer-related complications. Some evidence suggests a potential for prolonging survival, although available data are limited [6]. These approaches and their rationale are discussed here.

Systemic therapy for metastatic breast cancer, consisting of chemotherapy, endocrine therapy and/or biologic therapies, and supportive care, is discussed elsewhere. (See "Overview of the approach to metastatic breast cancer".)

LOCAL MANAGEMENT OF THE PRIMARY IN A PATIENT WITH DE NOVO METASTASES AT THE TIME OF INITIAL DIAGNOSIS

Approach — The primary role of local treatment to the breast and/or regional nodes in patients with stage IV breast cancer is palliation. Patients with metastatic disease should be evaluated for possible management of the primary and/or regional nodes if it may control debilitating symptoms from the cancer (eg, locally advanced breast tumors causing pain, bleeding, ulceration, infection, and poor wound healing; or regional nodal disease causing pain, motor weakness, and sensory deficits from brachial plexus invasion, or lymphedema). It should be noted that systemic therapy can also be helpful in such situations, decreasing the size of the tumor and alleviating symptoms.

However, in general, for patients who are asymptomatic at the site of their locoregional disease, locoregional treatment with surgery and/or radiation therapy is not standard-of-care treatment given lack of clear evidence that this improves survival.

Deviations to this approach may be rarely made on a case-by-case basis in a multidisciplinary setting, although these instances are exceptional. For example, we have offered local management of the primary to patients with human epidermal growth factor receptor 2 (HER2)-positive disease who have a brisk and dramatic response to systemic therapy, or when systemic disease is well controlled with systemic therapy but the primary site is progressing. We may also do surgery in patients who are not symptomatic, but we are concerned may be symptomatic if they do not respond quickly, such as a primary breast mass that is amenable to resection and close to ulcerating. However, the decision to proceed with local management in a similar situation should take into account patient preferences and should be made in a multidisciplinary setting. In these rare cases, the anticipated outcome of the local therapy and its lack of effect on systemic disease should be discussed with the patient.

Evidence — Four prospective randomized trials have been conducted to evaluate the survival effect of surgical resection of the primary lesion. Three of these have not shown a statistically significant difference in overall survival (OS), while a fourth did. In two of these, quality-of-life (QOL) analyses either showed no difference or even worse outcome with primary tumor resection (table 1).

No statistically significant improvement in OS was observed with local management of the primary in the following trials, although locoregional control was typically improved:

In the multicenter ECOG-ACRIN 2108 (E2108) trial, 256 patients with de novo stage IV breast cancer who had been on systemic therapy for four to eight months without progression were randomly assigned to continued systemic therapy alone or to early local therapy (surgery, with or without adjuvant radiation), with subsequent resumption of systemic therapy [7]. The median OS was 53 months, with no difference in three-year OS rates (68 percent in both groups). The three-year rate of locoregional progression was higher among patients receiving systemic therapy only (40 versus 16 percent), but, despite this, these patients experienced similar or better QOL outcomes at various time points compared with those receiving early local therapy.

The multicenter phase III NCT01015625 trial from Austria randomly assigned 90 patients with stage IV breast cancer to surgical resection of the primary tumor and axillary dissection followed by systemic therapy versus systemic therapy alone. The trial was designed to enroll 254 subjects but closed prematurely due to poor accrual. At a median follow-up of 37.5 months, median survival was 35 months in the cohort treated with surgery compared with 55 months without surgery. These OS data were not statistically significant (HR 0.69, 95% CI 0.36-1.33). Surgery also did not confer benefits in time to distant metastasis, time to locoregional metastases, or improved QOL [8,9].

Similar results were observed in a single-institution trial from India, in which 350 women with de novo metastatic breast cancer who had resectable hormone receptor-positive disease or who achieved a partial or complete response to anthracycline-based chemotherapy were randomly assigned to surgery (mastectomy or breast-conserving surgery [BCS] with axillary dissection) and standard postoperative radiation versus no locoregional treatment [10]. At a median follow-up of 23 months, no statistically significant difference in OS was observed between the surgery versus control groups (19.2 versus 20.5 months; HR 1.04, 95% CI 0.81-1.34). Locoregional treatment was associated with improved locoregional progression-free survival (PFS; median not attained versus 18.2 months; HR 0.16, 95% CI 0.10-0.26) but shorter distant PFS (11.3 versus 19.8 months in the control group; HR 1.42, 95% CI 1.08-1.85). In this study, endocrine therapy, taxanes, and HER2-directed therapy were permitted when clinically appropriate; however, most eligible women did not receive these treatments. It is unclear whether locoregional therapy would have improved survival in these women if effective systemic treatments had been administered.

Contrasting results, however, were observed in a trial from Turkey:

In the Turkish trial, 274 women with de novo metastatic breast cancer were randomly assigned to local management (mastectomy, or BCS with radiation) followed by systemic therapy, versus systemic therapy only [11]. This design differed from some of the previous trials, in which patients were enrolled only if they achieved disease control or response on systemic therapy [10,12]. While there was no difference in three-year survival, patients who received locoregional therapy experienced an improvement in five-year survival (42 versus 24 percent; HR 0.66, 95% CI 0.49-0.88). However, the arms were not balanced according to biologic subtypes and other potential prognostic factors. Patients randomized to locoregional therapy had lower rates of triple-negative disease (7 versus 17 percent), and higher rates of hormone receptor-positive disease (86 versus 72 percent) and solitary bone metastases (34 versus 24 percent), raising the concern that they were in better prognostic categories before the intervention. In a post-hoc subgroup analysis, patients with hormone receptor-positive, HER2-negative disease; age younger than 55 years; and those with solitary bone metastases appeared to derive the greatest benefit from local management.

Several previous retrospective studies have suggested that women with stage IV breast cancer have improved survival with removal of the primary tumor, but interpretation and generalizability of these results are limited by selection bias [13-30]. The randomized trials discussed above are more informative regarding the effect of locoregional therapy to women who present with de novo metastases and new primary breast cancers. As such, we typically suggest against surgery in the majority of patients with stage IV breast cancer unless it is directed towards palliation and symptom management.

A multicenter phase III trial from Japan (JCOG-1017) with similar design as the E2108 trial has completed accrual [31].

LOCAL MANAGEMENT OF METASTASES — The goal of therapy for patients with distant metastases is, in general, palliation. Therefore, the standard of care is, for most patients, systemic therapy with complementary surgery or radiation as indicated for particularly worrisome problems, such as brain or spinal cord metastases or intractable bone pain or fractures.

Selection of patients for local therapy to the metastasis

Patients who have severe pain at diagnosis of metastatic disease, or who have intractable pain in spite of systemic therapy for metastases, are usually considered candidates for radiation therapy to the affected site.

Metastases in certain sites are considered medical emergencies and are an indication for surgery and/or radiation. These include spinal cord or cauda equina compression, mass effect due to brain metastases, and impending or present pathologic fracture due to a bony metastasis. The primary objective of these treatments is palliative to control symptoms and to stabilize the patient.

Metastases to the chest wall are also usually treated with locoregional therapy, principally with the intent of avoiding future symptoms. Local therapy such as excision and radiation may also be helpful in patients with hemorrhagic chest wall lesions.

In patients with prior radiation to such an area, secondary radiation may be considered, although there is a high risk of additional skin complications. Alternatively, hyperthermia has been reported to be of value in previously irradiated areas, although this modality is not widely available. (See "Surgery and radiation for locoregional recurrences of breast cancer", section on 'Hyperthermia plus conventional RT'.)

Additionally, for patients with a first presentation of apparent metastatic disease, biopsy of an accessible metastatic site should be performed to confirm the diagnosis and re-establish receptor status. In some cases, a surgical approach may be appropriate (eg, wedge resection of a solitary pulmonary nodule or intracranial metastasis) rather than a biopsy by interventional radiology, and might also serve a treatment function. (See "Overview of the approach to metastatic breast cancer", section on 'Biopsy of metastatic lesion'.)

For other patients, who lack symptoms from their locoregional and distant disease,

With incidentally discovered asymptomatic central nervous system (CNS) involvement, local therapy is typically suggested (see below). This is unusual, however, given that screening of the CNS in patients without CNS symptoms is not routine in patients with metastatic breast cancer. (See 'Brain' below and "Brain metastases in breast cancer", section on 'Choosing between options'.)

With metastases in other sites, we suggest systemic treatment alone for most asymptomatic patients and reserve local therapies for symptomatic progression.

Exceptions may be made in rare instances, upon multidisciplinary discussion, for select patients with multiple good prognostic factors (eg, good performance status, fewer than three metastases, long disease-free interval between definitive treatment of the primary and development of distant oligometastasis, and high likelihood of complete resection) [6,32-42]. However, patients with good prognostic factors such as these are likely to have extended periods of survival regardless of whether they are offered surgery or not, and as such, systemic therapy alone remains the standard approach, even in these patients.

As examples of available data, in preliminary results of a randomized trial in 125 patients with ≤4 extracranial metastases from breast cancer, the addition of metastasis directed stereotactic body radiation therapy (SBRT) to standard of care systemic therapy failed to improve median progression-free survival (PFS; 19.5 months with SBRT versus 23 months without SBRT) or overall survival (OS; 36-month OS rates of 69 and 72 percent, respectively) [43]. Similarly, in a randomized trial in patients with oligometastatic non-small cell lung cancer or breast cancer, there was no demonstrated PFS or OS benefit with the addition of SBRT to standard systemic treatments among the 47 patients with breast cancer [36]. Only a single randomized trial in patients with all cancer types (including breast) has suggested a survival benefit to aggressive local treatment of metastases [37]. However, this study is relatively small and only contained very few patients with metastases from breast cancer. Data that are largely observational have suggested a survival benefit for aggressive local therapy in patients with oligometastatic disease [6,22,32-35]. However, selection bias is likely to have played a role in these studies.

Techniques for local management — For patients with metastatic breast cancer undergoing local therapy, surgery, radiation therapy, or both is primarily employed.

Radiation therapy techniques should be individualized with the aim of providing adequate coverage of the disease and minimizing exposure of adjacent normal tissue and organs at risk. Depending on the clinical situation, radiation therapy techniques that may be considered include SBRT for oligometastases, or conventional external-beam radiation therapy (EBRT) with simple one- to two-beam arrangements or more complex multibeam techniques, depending on the clinical situation and therapeutic goals. Radiofrequency ablation (RFA, typically with surgery) is a one-time treatment that has been examined as an alternative to SBRT for select, small hepatic tumors, and is discussed below. Indications for each modality, according to anatomic site, are discussed later in this topic. (See 'Indications by site' below.)

Further discussion of the technique of SBRT is found separately. (See "Radiation therapy techniques in cancer treatment", section on 'Stereotactic radiation therapy techniques'.)

All patients treated with local therapy should also receive appropriate systemic therapy. (See "Systemic therapy for locoregionally recurrent breast cancer".)

Indications by site

Brain — For most patients with brain metastases, a local approach such as surgical resection, stereotactic radiosurgery (SRS), or whole-brain radiotherapy should be employed, irrespective of whether the patient is symptomatic or not, often prior to or in conjunction with systemic therapy. However, an exception may be made in select patients with limited intracranial disease from human epidermal growth factor receptor 2 (HER2)-positive breast cancer, as systemic therapy alone may be a reasonable option in some cases. (See "Brain metastases in breast cancer", section on 'Choosing between options'.)

The approach to systemic therapy in patients with isolated brain metastases and no systemic disease is discussed elsewhere. (See "Brain metastases in breast cancer", section on 'Systemic therapy'.)

Patients with multiple metastatic deposits or extensive leptomeningeal disease are treated with whole-brain radiation therapy. For cases with more limited intracranial disease, when possible, SRS is used instead of whole-brain radiation to reduce toxicity. The risk factors, prognosis, and management of brain metastases in breast cancer are discussed separately. (See "Brain metastases in breast cancer" and "Overview of the treatment of brain metastases" and "Treatment of leptomeningeal disease from solid tumors".)

Ophthalmic structures — The prevalence of metastases involving the eyes in patients with metastatic breast cancer has been variably reported as ranging from 5 percent in asymptomatic patients to 38 percent in patients with visual symptoms [38,39]. The most common site of ophthalmic metastasis from breast cancer is the choroid [40]. Less common sites include the iris, ciliary body, optic nerve, optic disc, orbital bone and soft tissues, extraocular muscles, retina, and vitreous body. While presenting symptoms such as blurred vision, diplopia, floaters, field defect, and eye pain or discomfort may be nonspecific and may be attributed to some systemic therapy drugs or other malignant and nonmalignant causes, prompt referral for ophthalmology assessment is critical as loss of vision is a devastating outcome that may be avoided by timely investigation and treatment.

Local therapy decisions for choroidal metastases should be multidisciplinary, with the goals of preserving visual function, controlling pain, and avoiding tumor progression that may require enucleation. In patients with ophthalmic metastases, brain computed tomography (CT) and magnetic resonance imaging (MRI) should also be performed to rule out concomitant brain metastasis. A prospective study of patients with choroidal metastasis reported that the rate of brain metastasis identified on CT with contrast was 26 percent [41].

In patients who are asymptomatic, systemic therapy with careful observation is an option [42].

In patients with symptoms, palliative EBRT sparing the lens and anterior chamber is the most common modality demonstrated to be safe and effective.

A prospective study from the German Cancer Society reported outcomes in 50 patients with choroidal metastases treated with EBRT 40 Gy in 20 fractions using a single lateral beam for unilateral disease and parallel opposed lateral beams for bilateral disease [44]. Visual function improved in 36 percent and stabilized in 50 percent of cases. On ultrasound follow-up, complete regression was observed in 38 percent and partial regression in 44 percent of cases.

In the palliative setting, shorter EBRT courses over 5 to 10 fractions may also be considered. In a study of 123 patients with choroidal metastases, 71 percent of whom had breast cancer, the most commonly used regimen was 30 Gy in 10 fractions. Visual improvement was observed in 55 percent of cases after EBRT and 80 percent of cases after chemotherapy plus EBRT [45]. Similarly, in a series of 55 patients with 71 affected eyes treated with EBRT 20 Gy in five fractions, visual acuity was stable or improved in 80 percent, tumor regressed in 91 percent, and complete response was observed in 67 percent of affected eyes [46].

Local treatment alternatives to conventional EBRT include proton therapy, plaque brachytherapy, photodynamic therapy, and intravitreal injection of anti-vascular endothelial growth factor (VEGF) [47]. Proton therapy allows highly focused tumor targeting with preservation of normal adjacent tissues [48,49]. Plaque brachytherapy entails applying a radioactive plaque, most commonly Iodine-125 or Palladium-103, to the sclera to deliver radiation over a short distance to the target while sparing the lens and retina [47]. Proton therapy and plaque brachytherapy, however, are less commonly used in the setting of metastatic breast cancer than EBRT, as they are not as widely available and are generally reserved for more radioresistant tumors such as sarcoma and melanoma. Photodynamic therapy and intravitreal injections of anti-VEGF are less invasive office-based treatments that may be offered by ophthalmologists, but data reporting outcomes specific to the metastatic breast cancer setting are limited to case reports and small case series [47].

Bone

Indications for local management – Indications for local management of bone disease are spinal cord or cauda equina compression, pathologic fracture or impending fracture, significant pain, or decreased mobility of a joint.

Specific approaches are discussed below.

Surgery – Pathologic fractures, impending fractures, or epidural spinal cord or nerve compression may require surgical intervention. For asymptomatic patients without evidence of impending fracture, there is no clear role for resection. When metastatic breast cancer is confined to the bones, the natural history is usually characterized by an indolent course and good response to systemic therapy [50-52]. One UpToDate expert (MS) views a solitary sternal metastasis as a possible exception, given that sternal metastases may remain solitary for a long time and may represent a locoregional recurrence rather than true metastatic disease [53,54]. However, the other UpToDate experts note that sternal resection is associated with morbidity and risk of poor cosmesis and has not been shown to improve survival, and therefore do not favor this approach over less invasive options such as surveillance on systemic therapy or local treatment with radiation therapy. (See 'Selection of patients for local therapy to the metastasis' above.)

Radiation – In cases with painful bone (spinal and extraspinal) metastases, short-course, local-field external-beam palliative radiotherapy using single or multiple fractions is commonly used, supported by a large body of prospective data demonstrating its safety and palliative efficacy [55,56]. The role of more complex radiation techniques such as SBRT in breast cancer patients with bone metastases, including those with limited-volume disease, remains to be defined by prospective trial data and is discussed separately. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Selection of definitive treatment' and "Radiation therapy for the management of painful bone metastases".)

Minimally invasive, image-guided percutaneous techniques – Interventional radiology and anesthesiology are disciplines that can offer useful adjunctive local procedures to palliate patients with symptomatic bone metastases, including patients who have recurrent or intractable pain despite radiation therapy. Minimally invasive, image-guided percutaneous techniques such as vertebroplasty, kyphoplasty, cementoplasty, thermal ablation, and neurolysis can provide durable pain control and stabilization for both spinal and nonspinal bone metastases and may be considered for carefully selected patients with interdisciplinary review and operator expertise [57-59]. (See "Overview of therapeutic approaches for adult patients with bone metastasis from solid tumors" and "Image-guided ablation of skeletal metastases".)

Systemic therapy and adjunctive treatments – As in other metastatic sites, systemic therapy can improve symptoms and progression of bone metastases. Bisphosphonates, other osteoclast inhibitors, and radioisotope therapy reduce the morbidity of metastatic bone disease, in particular skeletal-related events, which include fracture, need for surgery or radiation to bone, spinal cord compression, and hypercalcemia of malignancy.

(See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors".)

(See "Radiation therapy for the management of painful bone metastases".)

(See "Treatment and prognosis of neoplastic epidural spinal cord compression".)

Lung — Lung metastases that are asymptomatic generally do not require local intervention, while those that are symptomatic or pose urgent risks to pulmonary function such as intrinsic or extrinsic airway obstruction and superior vena cava obstruction may benefit from prompt local treatments. For some patients, pulmonary resection may be diagnostic as well as palliative, since a significant number of solitary pulmonary nodules in patients with a history of breast cancer are not breast cancer metastases [60-62]. Patients evaluated for lung resection should have a complete pulmonary evaluation. (See "Diagnostic evaluation of the incidental pulmonary nodule" and 'Selection of patients for local therapy to the metastasis' above.)

As discussed above, metastasectomy for therapeutic purposes has been reported to occasionally be associated with long-term survival [6,32,33,63]. It must be noted, however, that patients who experience such apparent benefit have a favorable prognosis, regardless of whether surgery is done; therefore, most UpToDate experts prefer to avoid the morbidity and mortality associated with such procedures, particularly in the absence of randomized data. Case series suggest five-year overall survival (OS) ranging from 30 to 80 percent and median survival duration ranging from 40 to 100 months among select breast cancer patients undergoing resection of pulmonary metastases [32,60,63-65]. A meta-analysis of 16 retrospective studies with almost 2000 patients reported a five-year survival rate of 46 percent after resection of isolated lung metastases [66]. Adverse prognostic features were short DFI <3 years, >1 metastatic lesion, and negative hormone receptor status. (See "Surgical resection of pulmonary metastases: Outcomes by histology".)

Other approaches in the local management of lung metastases include EBRT, typically for lung or mediastinal/hilar masses causing extrinsic airway obstruction, peripheral or pleural disease-causing chest wall pain, or apical masses extending into spinal canal or brachial plexus; endobronchial brachytherapy for intrinsic bronchial obstruction; SBRT; and RFA, although central lesions may be difficult to reach by RFA. The local management of lung metastases, including each of these modalities, is discussed separately.

(See "Diagnostic evaluation of the incidental pulmonary nodule".)

(See "Endobronchial brachytherapy".)

(See "Stereotactic body radiation therapy for lung tumors".)

(See "Image-guided ablation of lung tumors".)

Liver — Hepatic metastases occur in over one-half of patients with metastatic breast cancer. They are most commonly a late development, associated with disseminated disease and a poorer prognosis than bone or soft tissue metastases. Only 5 to 12 percent of patients have isolated liver involvement [67-69].

Indications for local management – Indications for local management of liver metastases include pain, bleeding that is refractory to medical therapy, or biliary obstruction.

Some UpToDate experts also offer local resection in carefully selected, asymptomatic patients, although there are no prospective data comparing local therapy with the administration of systemic treatment. Proponents of this approach identify candidates as those with isolated liver involvement (5 to 12 percent of patients with metastatic breast cancer [67-69]), particularly those with hormone-positive disease, who have normal liver function, good performances status, and have had a long DFI [6,70,71]. However, such patients are likely to have a good prognosis regardless of whether they undergo surgery, so most UpToDate experts prefer to treat with systemic therapy only in the absence of urgent or palliative indication. (See 'Selection of patients for local therapy to the metastasis' above.)

Approaches for local management – Hepatic resection and SBRT are the most frequently employed methods of ablating liver metastases in carefully selected patients. The selection of SBRT versus surgery depends on which modality will result in the highest probability of preserving liver function. For larger (>5 cm) peripheral lesions, surgery can sometimes preserve more functional liver than SBRT. By contrast, for central lesions, SBRT may be preferred. RFA has been explored as another option for tumors <3 cm that are not close to major vessels, biliary structures, or the diaphragm [72]. While there are only retrospective data reporting outcomes after RFA in patients with metastatic breast cancer, these data suggest local efficacy particularly for solitary hepatic lesions smaller than 3 cm in diameter [72-77].

Although we do not suggest their routine use based on available data, alternative local therapies are being explored to treat liver metastases, including selective internal radiation therapy, percutaneous ethanol injection, cryotherapy, hepatic arterial infusion chemotherapy, transhepatic arterial chemoembolization, and interstitial laser therapy [78,79]. In general, there are fewer data regarding the use of these techniques for metastatic breast cancer than there are for patients with liver metastases from colorectal cancer or with primary hepatocellular cancer. Furthermore, none of these methods has been directly compared with systemic chemotherapy in metastatic breast cancer.

Outcomes with local therapy – The data to support local therapy for liver metastases were derived from a systematic review of 19 retrospective studies including 535 patients who underwent hepatectomy for metastatic breast cancer [80]. Hepatectomy was undertaken in patients with mostly solitary lesions or with a median of two lesions (range, one to four). The median OS was 40 months (range, 23 to 77 months) with a five-year survival following resection of 40 percent (range, 21 to 80 percent) [80]. Postoperative mortality ranged from 0 to 6 percent, and the complication rate ranged from 0 to 44 percent. Poor prognostic factors following hepatic resection include positive margins and hormone-refractory disease.

In a subsequent case-control retrospective study of 167 patients, 69 of whom received surgery and/or ablation and 98 of whom were treated medically, OS between the two groups was not significantly different (50 versus 45 months in the local treatment versus medical treatment groups, respectively) [81]. Local treatment was associated with a recurrence-free interval of 28.5 months. Those receiving local treatment had lower-risk disease, with a higher frequency of estrogen receptor positivity, lower median number of liver metastases, and a longer interval between breast cancer diagnosis and solitary liver metastasis presentation (53 versus 30 months). These results suggest that among patients with favorable-risk disease, local treatment may provide a significant period of disease-free survival and time off from systemic chemotherapy. (See "Overview of hepatic resection" and "Open hepatic resection techniques".)

However, as noted, it is highly likely that patients who are chosen for local therapies are selected for otherwise favorable prognostic factors, including isolated and usually single metastases, often with hormone receptor-positive disease, and it is unclear if apparent favorable OS is due to, or in spite of, the therapy.

Gastrointestinal tract — Gastrointestinal (GI) tract metastases are infrequently encountered in practice, although autopsy series have reported rates ranging from 8 to 30 percent [82,83]. Invasive lobular cancers have a higher propensity to metastasize to the GI tract compared with other histologies [84-86], as may hormone receptor-positive cancers, irrespective of histology [86]. The most common sites of GI metastases from breast cancer are the stomach and colon, while esophageal and small intestine metastases are possible but less common. Often, these metastases to unusual sites originate from lobular infiltrating cancers of the breast.

As GI metastases can occur many years after an initial breast cancer diagnosis, and given that some can respond to chemotherapy and endocrine therapy depending on biomarkers, patients with unexplained GI symptoms should be referred to gastroenterology for thorough evaluation of the abdomen and GI tract, with biopsy of any suspicious lesions seen on endoscopy to differentiate metastatic breast cancer from other entities such as primary GI cancer, lymphoma, or benign disease and to guide appropriate treatment.

In cases with confirmed GI metastases causing obstruction, bleeding or intractable pain, and in which a targetable lesion can be identified, involved-field palliative EBRT may be considered for symptom control. Other local modalities in symptomatic patients include palliative surgical bypass, percutaneous enterostomy, or endoscopic stenting. The choice of local procedure should be made in a multidisciplinary setting with consideration of the clinical scenario and patient's goals of care.

Ovaries — Although the ovaries are also a rare site for metastases from breast cancer [87,88], limited data suggest ovarian breast cancer metastases can appear many years following the initial diagnosis of breast cancer, often originating from lobular primary cancers [89-92]. Surgical evaluation of an adnexal mass may be required to differentiate metastatic breast cancer from a primary ovarian cancer. Furthermore, for premenopausal patients with hormone receptor-positive breast cancer, oophorectomy can provide a therapeutic effect, regardless of whether metastatic disease to the ovaries is present or not. (See "Approach to the patient with an adnexal mass", section on 'Scope of surgery' and "Treatment for hormone receptor-positive, HER2-negative advanced breast cancer", section on 'Additional considerations for premenopausal women'.)

Other indications for local management of ovarian metastases may include pain or bleeding that is refractory to medical therapy, although in practice this presentation is rare.

Data are limited in regards to local management of ovarian metastases from breast cancer. In one series of 147 patients with metastatic disease to the ovary (8 percent of whom had a breast primary), the median OS after ovarian metastasectomy was 41 months [93]. For the entire series, massive intraoperative ascites, multiple metastases, and locally invasive disease were independent factors for a poorer OS.

INTEGRATING SYSTEMIC THERAPY WITH LOCAL TREATMENT — All patients who undergo local management of metastatic breast cancer should also receive systemic therapy.

Whether or not next-line therapy is chosen depends upon whether the line of treatment the patient was previously receiving was well tolerated, and whether it was controlling disease that was not addressed by local therapy. For example, if a patient with hormone receptor positive, human epidermal growth factor receptor 2 (HER2)-negative disease experienced progression intracranially on a well-tolerated endocrine agent but had stable systemic disease, it would be reasonable to manage the brain lesions with radiation and continue the given line of endocrine therapy. However, if progression occurred systemically as well, or if the present line of therapy was poorly tolerated, next-line systemic therapy should be offered. (See "Overview of the approach to metastatic breast cancer".)

For patients who will receive systemic therapy with endocrine agents or immunotherapy, treatment is usually continued concurrently with radiation. However, chemotherapy and targeted agents such as cyclin-dependent kinase 4/6 inhibitors are typically held for radiation and resumed several days after completion.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Breast cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Treatment of metastatic breast cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Patients with metastatic breast cancer are unlikely to be cured of their disease by any means, and the goal of treatment is principally palliative in nature. (See 'Introduction' above.)

Although systemic therapy is the mainstay of treatment for metastatic breast cancer, local management of the primary as well as metastasis-specific local treatment may palliate existing symptoms and improve local progression-free survival. Further data are required to clarify the effect on overall survival. (See 'Introduction' above.)

The primary role of local treatment to the breast in metastatic breast cancer is palliation. In general, for patients who are asymptomatic at the site of their primary with no threat to organ function, we suggest systemic therapy alone rather than local treatment and systemic therapy (Grade 2C), given a lack of clear evidence that it improves survival. However, exceptions may be made in rare instances, upon multidisciplinary discussion. (See 'Local management of the primary in a patient with de novo metastases at the time of initial diagnosis' above.)

For the first presentation of metastatic disease, biopsy of the metastatic site should be performed to confirm the diagnosis and re-establish receptor status. (See "Overview of the approach to metastatic breast cancer", section on 'Biopsy of metastatic lesion'.)

Patients who present with symptomatic metastases, eg, intractable pain, bleeding, loss of organ function, or an oncologic emergency (eg, cord compression, mass effect due to brain metastases, pathologic fracture due to a bony metastasis), are appropriate candidates for urgent local intervention to relieve symptoms and preserve function and quality of life. (See 'Indications by site' above.)

For asymptomatic patients, local management may be appropriate in select situations, for example, for the patient with an undiagnosed lung nodule or the patient with one or more brain metastases. Outside of these situations, most UpToDate experts manage asymptomatic metastatic disease with systemic therapy only and reserve local therapies for symptomatic progression, while a few UpToDate experts may offer local management to select patients with multiple good-risk features, although this is not considered standard of care. (See 'Indications by site' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Julia White, MD, who contributed to an earlier version of this topic review.

  1. Chia SK, Speers CH, D'yachkova Y, et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer 2007; 110:973.
  2. Koleva-Kolarova RG, Oktora MP, Robijn AL, et al. Increased life expectancy as a result of non-hormonal targeted therapies for HER2 or hormone receptor positive metastatic breast cancer: A systematic review and meta-analysis. Cancer Treat Rev 2017; 55:16.
  3. Dawood S, Haaland B, Albaracin C, et al. Is the Proportion of Patients Diagnosed with Synchronous Stage IV Breast Cancer Who Survive More than Two Years Increasing over Time? Oncology 2015; 89:79.
  4. Gobbini E, Ezzalfani M, Dieras V, et al. Time trends of overall survival among metastatic breast cancer patients in the real-life ESME cohort. Eur J Cancer 2018; 96:17.
  5. Fietz T, Tesch H, Rauh J, et al. Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer - Results from the prospective German TMK cohort study. Breast 2017; 34:122.
  6. Pagani O, Senkus E, Wood W, et al. International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst 2010; 102:456.
  7. Khan SA, Zhao F, Goldstein LJ, et al. Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108). J Clin Oncol 2022; 40:978.
  8. Fitzal F, Bjelic-Radisic V, Knauer M, et al. Impact of Breast Surgery in Primary Metastasized Breast Cancer: Outcomes of the Prospective Randomized Phase III ABCSG-28 POSYTIVE Trial. Ann Surg 2019; 269:1163.
  9. Bjelic-Radisic V, Fitzal F, Knauer M, et al. Primary surgery versus no surgery in synchronous metastatic breast cancer: patient-reported quality-of-life outcomes of the prospective randomized multicenter ABCSG-28 Posytive Trial. BMC Cancer 2020; 20:392.
  10. Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 2015; 16:1380.
  11. Soran A, Ozmen V, Ozbas S, et al. Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01. Ann Surg Oncol 2018; 25:3141.
  12. Khan SA, Zhao F, Solin LJ, et al. A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108). J Clin Oncol 2020; 38S: ASCO #LBA2.
  13. Harris E, Barry M, Kell MR. Meta-analysis to determine if surgical resection of the primary tumour in the setting of stage IV breast cancer impacts on survival. Ann Surg Oncol 2013; 20:2828.
  14. Warschkow R, Güller U, Tarantino I, et al. Improved Survival After Primary Tumor Surgery in Metastatic Breast Cancer: A Propensity-adjusted, Population-based SEER Trend Analysis. Ann Surg 2016; 263:1188.
  15. Carmichael AR, Anderson ED, Chetty U, Dixon JM. Does local surgery have a role in the management of stage IV breast cancer? Eur J Surg Oncol 2003; 29:17.
  16. Nieto Y, Cagnoni PJ, Shpall EJ, et al. Phase II trial of high-dose chemotherapy with autologous stem cell transplant for stage IV breast cancer with minimal metastatic disease. Clin Cancer Res 1999; 5:1731.
  17. Juan O, Lluch A, de Paz L, et al. Prognostic factors in patients with isolated recurrences of breast cancer (stage IV-NED). Breast Cancer Res Treat 1999; 53:105.
  18. Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery 2002; 132:620.
  19. Rapiti E, Verkooijen HM, Vlastos G, et al. Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol 2006; 24:2743.
  20. Babiera GV, Rao R, Feng L, et al. Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and an intact primary tumor. Ann Surg Oncol 2006; 13:776.
  21. Gnerlich J, Jeffe DB, Deshpande AD, et al. Surgical removal of the primary tumor increases overall survival in patients with metastatic breast cancer: analysis of the 1988-2003 SEER data. Ann Surg Oncol 2007; 14:2187.
  22. Fields RC, Jeffe DB, Trinkaus K, et al. Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage IV breast cancer after controlling for site of metastasis. Ann Surg Oncol 2007; 14:3345.
  23. Blanchard DK, Shetty PB, Hilsenbeck SG, Elledge RM. Association of surgery with improved survival in stage IV breast cancer patients. Ann Surg 2008; 247:732.
  24. Hazard HW, Gorla SR, Scholtens D, et al. Surgical resection of the primary tumor, chest wall control, and survival in women with metastatic breast cancer. Cancer 2008; 113:2011.
  25. Cady B, Nathan NR, Michaelson JS, et al. Matched pair analyses of stage IV breast cancer with or without resection of primary breast site. Ann Surg Oncol 2008; 15:3384.
  26. Thomas A, Khan SA, Chrischilles EA, Schroeder MC. Initial Surgery and Survival in Stage IV Breast Cancer in the United States, 1988-2011. JAMA Surg 2016; 151:424.
  27. Leung AM, Vu HN, Nguyen KA, et al. Effects of surgical excision on survival of patients with stage IV breast cancer. J Surg Res 2010; 161:83.
  28. Ruiterkamp J, Ernst MF, van de Poll-Franse LV, et al. Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis. Eur J Surg Oncol 2009; 35:1146.
  29. Xiao W, Zou Y, Zheng S, et al. Primary tumor resection in stage IV breast cancer: A systematic review and meta-analysis. Eur J Surg Oncol 2018; 44:1504.
  30. Bilani N, Yaghi M, Singh Jabbal I, et al. Survival benefit of a combined surgical approach in patients with metastatic breast cancer. J Surg Oncol 2021; 124:1235.
  31. Shien T, Nakamura K, Shibata T, et al. A randomized controlled trial comparing primary tumour resection plus systemic therapy with systemic therapy alone in metastatic breast cancer (PRIM-BC): Japan Clinical Oncology Group Study JCOG1017. Jpn J Clin Oncol 2012; 42:970.
  32. Friedel G, Pastorino U, Ginsberg RJ, et al. Results of lung metastasectomy from breast cancer: prognostic criteria on the basis of 467 cases of the International Registry of Lung Metastases. Eur J Cardiothorac Surg 2002; 22:335.
  33. Friedel G, Linder A, Toomes H. The significance of prognostic factors for the resection of pulmonary metastases of breast cancer. Thorac Cardiovasc Surg 1994; 42:71.
  34. Ly BH, Nguyen NP, Vinh-Hung V, et al. Loco-regional treatment in metastatic breast cancer patients: is there a survival benefit? Breast Cancer Res Treat 2010; 119:537.
  35. Lehrer EJ, Singh R, Wang M, et al. Safety and Survival Rates Associated With Ablative Stereotactic Radiotherapy for Patients With Oligometastatic Cancer: A Systematic Review and Meta-analysis. JAMA Oncol 2021; 7:92.
  36. Tsai CJ, Yang JT, Shaverdian N, et al. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet 2024; 403:171.
  37. Palma DA, Olson R, Harrow S, et al. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol 2020; 38:2830.
  38. Wiegel T, Kreusel KM, Bornfeld N, et al. Frequency of asymptomatic choroidal metastasis in patients with disseminated breast cancer: results of a prospective screening programme. Br J Ophthalmol 1998; 82:1159.
  39. Mewis L, Young SE. Breast carcinoma metastatic to the choroid. Analysis of 67 patients. Ophthalmology 1982; 89:147.
  40. Georgalas I, Paraskevopoulos T, Koutsandrea C, et al. Ophthalmic Metastasis of Breast Cancer and Ocular Side Effects from Breast Cancer Treatment and Management: Mini Review. Biomed Res Int 2015; 2015:574086.
  41. Bottke D, Wiegel T, Kreusel KM, et al. Is a diagnostic CT of the brain indicated in patients with choroidal metastases before radiotherapy? Strahlenther Onkol 2005; 181:251.
  42. Demirci H, Shields CL, Chao AN, Shields JA. Uveal metastasis from breast cancer in 264 patients. Am J Ophthalmol 2003; 136:264.
  43. et al, Chmura S, Winter KA, Woodward WA. NRG-BR002: A phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557). J Clin Oncol 2022; 40:ASCO #1007.
  44. Wiegel T, Bottke D, Kreusel KM, et al. External beam radiotherapy of choroidal metastases--final results of a prospective study of the German Cancer Society (ARO 95-08). Radiother Oncol 2002; 64:13.
  45. d'Abbadie I, Arriagada R, Spielmann M, Lê MG. Choroid metastases: clinical features and treatments in 123 patients. Cancer 2003; 98:1232.
  46. Hahn E, Laperriere N, Krema H, et al. Clinical outcomes of hypofractionated radiation therapy for choroidal metastases: Symptom palliation, tumor control, and survival. Pract Radiat Oncol 2017; 7:388.
  47. Mathis T, Jardel P, Loria O, et al. New concepts in the diagnosis and management of choroidal metastases. Prog Retin Eye Res 2019; 68:144.
  48. Tsina EK, Lane AM, Zacks DN, et al. Treatment of metastatic tumors of the choroid with proton beam irradiation. Ophthalmology 2005; 112:337.
  49. Kamran SC, Collier JM, Lane AM, et al. Outcomes of proton therapy for the treatment of uveal metastases. Int J Radiat Oncol Biol Phys 2014; 90:1044.
  50. Briasoulis E, Karavasilis V, Kostadima L, et al. Metastatic breast carcinoma confined to bone: portrait of a clinical entity. Cancer 2004; 101:1524.
  51. Sherry MM, Greco FA, Johnson DH, Hainsworth JD. Metastatic breast cancer confined to the skeletal system. An indolent disease. Am J Med 1986; 81:381.
  52. Coleman RE, Smith P, Rubens RD. Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer 1998; 77:336.
  53. Noguchi S, Miyauchi K, Nishizawa Y, et al. Results of surgical treatment for sternal metastasis of breast cancer. Cancer 1988; 62:1397.
  54. Noble J, Sirohi B, Ashley S, et al. Sternal/para-sternal resection for parasternal local recurrence in breast cancer. Breast 2010; 19:350.
  55. Lutz S, Balboni T, Jones J, et al. Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline. Pract Radiat Oncol 2017; 7:4.
  56. Chow R, Hoskin P, Schild SE, et al. Single vs multiple fraction palliative radiation therapy for bone metastases: Cumulative meta-analysis. Radiother Oncol 2019; 141:56.
  57. Tomasian A, Jennings JW. Percutaneous Interventional Techniques for Treatment of Spinal Metastases. Semin Intervent Radiol 2020; 37:192.
  58. Ahmed O, Feinberg N, Lea WB. Interventional Techniques for the Ablation and Augmentation of Extraspinal Lytic Bone Metastases. Semin Intervent Radiol 2019; 36:221.
  59. Hayek G, Kastler B. Interventional radiology for treatment of bone metastases. Cancer Radiother 2020; 24:374.
  60. McDonald ML, Deschamps C, Ilstrup DM, et al. Pulmonary resection for metastatic breast cancer. Ann Thorac Surg 1994; 58:1599.
  61. Cahan WG, Castro EB. Significance of a solitary lung shadow in patients with breast cancer. Ann Surg 1975; 181:137.
  62. Casey JJ, Stempel BG, Scanlon EF, Fry WA. The solitary pulmonary nodule in the patient with breast cancer. Surgery 1984; 96:801.
  63. Planchard D, Soria JC, Michiels S, et al. Uncertain benefit from surgery in patients with lung metastases from breast carcinoma. Cancer 2004; 100:28.
  64. Yoshimoto M, Tada K, Nishimura S, et al. Favourable long-term results after surgical removal of lung metastases of breast cancer. Breast Cancer Res Treat 2008; 110:485.
  65. Meimarakis G, Rüttinger D, Stemmler J, et al. Prolonged overall survival after pulmonary metastasectomy in patients with breast cancer. Ann Thorac Surg 2013; 95:1170.
  66. Fan J, Chen D, Du H, et al. Prognostic factors for resection of isolated pulmonary metastases in breast cancer patients: a systematic review and meta-analysis. J Thorac Dis 2015; 7:1441.
  67. Hoe AL, Royle GT, Taylor I. Breast liver metastases--incidence, diagnosis and outcome. J R Soc Med 1991; 84:714.
  68. Atalay G, Biganzoli L, Renard F, et al. Clinical outcome of breast cancer patients with liver metastases alone in the anthracycline-taxane era: a retrospective analysis of two prospective, randomised metastatic breast cancer trials. Eur J Cancer 2003; 39:2439.
  69. Zinser JW, Hortobagyi GN, Buzdar AU, et al. Clinical course of breast cancer patients with liver metastases. J Clin Oncol 1987; 5:773.
  70. Pocard M, Pouillart P, Asselain B, et al. [Hepatic resection for breast cancer metastases: results and prognosis (65 cases)]. Ann Chir 2001; 126:413.
  71. Selzner M, Morse MA, Vredenburgh JJ, et al. Liver metastases from breast cancer: long-term survival after curative resection. Surgery 2000; 127:383.
  72. Veltri A, Gazzera C, Barrera M, et al. Radiofrequency thermal ablation (RFA) of hepatic metastases (METS) from breast cancer (BC): an adjunctive tool in the multimodal treatment of advanced disease. Radiol Med 2014; 119:327.
  73. Pawlik TM, Izzo F, Cohen DS, et al. Combined resection and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 2003; 10:1059.
  74. Livraghi T, Goldberg SN, Solbiati L, et al. Percutaneous radio-frequency ablation of liver metastases from breast cancer: initial experience in 24 patients. Radiology 2001; 220:145.
  75. Bortolotto C, Macchi S, Veronese L, et al. Radiofrequency ablation of metastatic lesions from breast cancer. J Ultrasound 2012; 15:199.
  76. Wood TF, Rose DM, Chung M, et al. Radiofrequency ablation of 231 unresectable hepatic tumors: indications, limitations, and complications. Ann Surg Oncol 2000; 7:593.
  77. de Baere T, Elias D, Dromain C, et al. Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR Am J Roentgenol 2000; 175:1619.
  78. Wong J, Cooper A. Local Ablation for Solid Tumor Liver Metastases: Techniques and Treatment Efficacy. Cancer Control 2016; 23:30.
  79. Hansen PD, Cassera MA, Wolf RF. Ablative technologies for hepatocellular, cholangiocarcinoma, and metastatic colorectal cancer of the liver. Surg Oncol Clin N Am 2015; 24:97.
  80. Chua TC, Saxena A, Liauw W, et al. Hepatic resection for metastatic breast cancer: a systematic review. Eur J Cancer 2011; 47:2282.
  81. Sadot E, Lee SY, Sofocleous CT, et al. Hepatic Resection or Ablation for Isolated Breast Cancer Liver Metastasis: A Case-control Study With Comparison to Medically Treated Patients. Ann Surg 2016; 264:147.
  82. Washington K, McDonagh D. Secondary tumors of the gastrointestinal tract: surgical pathologic findings and comparison with autopsy survey. Mod Pathol 1995; 8:427.
  83. Caramella E, Bruneton JN, Roux P, et al. Metastases of the digestive tract. Report of 77 cases and review of the literature. Eur J Radiol 1983; 3:331.
  84. Taal BG, Peterse H, Boot H. Clinical presentation, endoscopic features, and treatment of gastric metastases from breast carcinoma. Cancer 2000; 89:2214.
  85. McLemore EC, Pockaj BA, Reynolds C, et al. Breast cancer: presentation and intervention in women with gastrointestinal metastasis and carcinomatosis. Ann Surg Oncol 2005; 12:886.
  86. Montagna E, Pirola S, Maisonneuve P, et al. Lobular Metastatic Breast Cancer Patients With Gastrointestinal Involvement: Features and Outcomes. Clin Breast Cancer 2018; 18:e401.
  87. Demopoulos RI, Touger L, Dubin N. Secondary ovarian carcinoma: a clinical and pathological evaluation. Int J Gynecol Pathol 1987; 6:166.
  88. Alvarado-Cabrero I, Rodríguez-Gómez A, Castelan-Pedraza J, Valencia-Cedillo R. Metastatic ovarian tumors: a clinicopathologic study of 150 cases. Anal Quant Cytopathol Histpathol 2013; 35:241.
  89. Quan ML, Fey J, Eitan R, et al. Role of laparoscopy in the evaluation of the adnexa in patients with stage IV breast cancer. Gynecol Oncol 2004; 92:327.
  90. Abu-Rustum NR, Aghajanian CA, Venkatraman ES, et al. Metastatic breast carcinoma to the abdomen and pelvis. Gynecol Oncol 1997; 66:41.
  91. Curtin JP, Barakat RR, Hoskins WJ. Ovarian disease in women with breast cancer. Obstet Gynecol 1994; 84:449.
  92. Bigorie V, Morice P, Duvillard P, et al. Ovarian metastases from breast cancer: report of 29 cases. Cancer 2010; 116:799.
  93. Li W, Wang H, Wang J, et al. Ovarian metastases resection from extragenital primary sites: outcome and prognostic factor analysis of 147 patients. BMC Cancer 2012; 12:278.
Topic 760 Version 42.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟