Maha Abu El Gassim1*, Ahmed Abdel Rahim2,Ayda Hussein OM3, Omer Elgaili YE4
1 Clinical Respiratory Medicine, University of Khartoum, Alneelain University, 52nd St, Khartoum, Sudan. 2 Associate Professor, General, Breast and Laparoscopic Surgeon, Alneelain University, Khartoum, Sudan. 3 Consultant Pulmonologist, Assistant Professor, Al Neellain University, Khartoum, Sudan.
*Corresponding Author:Maha Abu El Gassim, Clinical Respiratory Medicine, University of Khartoum, Alneelain University, 52nd St, Khartoum, Sudan, Tel: 5775066; Fax: 5775066; E-mail:firstname.lastname@example.org
Citation: Maha Abu El Gassim, Ahmed Abdel Rahim, Ayda Hussein OM, Omer Elgaili YE (2021) Evaluation of Thoracic Manifestations in Sudanese Patients with Breast Cancer. Cancer Prog Diagn 5: 123.
Received: March 25, 2021; Accepted: May 10, 2021; Published: May 16, 2021.
Copyright: © 2021 Maha Abu El Gassim, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Thoracic manifestations of breast cancer are most commonly related to metastases and can be observed in long time after the diagnosis of breast cancer.
Objectives: To evaluate the thoracic manifestations in Sudanese patients with breast cancer.
Methodology: This is a prospective descriptive cross-section hospital-based study, carried out during the period from January to September 2017 at private clinic of breast cancer of Dr. Ayda Hussein, Respiratory Department in Alshaab Teaching Hospital and Oncology Units at Alamel Tower, included all patients with breast cancer associated with thoracic abnormalities, which confirmed clinically and radiologically by chest X-ray and CT chest. The data was collected by questionnaire then analysed by computer using SPSS.
Results: A total of 70 patients with breast cancer were evaluated clinically and radiologic ally, 68 (97.1%) were females and 2 (2.9%) were males, the mean age was (49.91 ± 18.26) years, 39 (55.07%) were from Khartoum and 31 (44.93%) patients from outside Khartoum State, 47 (67.1%) patients not smokers, the time interval between the diagnosis of primary breast cancer and detection of thoracic manifestations was found to be 1-3 years in half of the study population 35 (50.0%), and
Conclusion: The thoracic manifestations in Sudanese patients with breast cancer were pleural effusion, metastases, pulmonary embolism, lymphangitis carcinomatosis, masses, cavity and fibrosis. The most common thoracic manifestations detected clinically among the study population were shortness of breath, cough and chest pain. The most common thoracic manifestations detected radiologically among the study population were pleural effusion and metastases.
Breast cancer is the second most common cause of cancer related death in women. The incidence and mortality of breast cancer have continuously increased over the last ten years, 60 – 74 % of patients dying of breast cancer have pulmonary metastases and the Lung is the only site of metastasis in 21 %.
Metastasis can occur both by hematogenous and lymphatic spread, however pulmonary problems may result also from treatment such as chemo-radiotherapy, infections or second primary malignancy. Most Breast cancer patients with intrathoracic metastases are asymptomatic, the exception being those with significant pleural effusions. Therefore, unless pleural parenchyma or nodal metastases are demonstrated at initial staging, thoracic metastases are most commonly found at the time of follow up imaging. 
A significant number  are found on chest X-rays done for other reasons. Cough, shortness of breath, chest pain and orthopnea are the most common clinical symptoms. Isolated involvement of the lung of pleural space occurs in 15% - 20 % of women with metastatic breast cancer .
The lung is a common site of metastasis and it may present with solitary or multiple nodules, lymphangitic metastasis, or airspace consolidation.. However, ground glass opacity (GGO) is a rare form of metastatic lung involvement and can be misdiagnosed as drug-induced pneumonitis or viral infection.
Lung metastases are usually peripheral and if large enough may be discovered on preoperative chest radiographs. Chest X-ray is the choice as a baseline study or in follow up, because of its low cost, however the extremely low yield and the false, positive results and low sensitivity compared with CT, that make the CT is the preferred modality for investigation of thoracic metastases. Pleural involvement may be suspected based on clinical signs on physical examination or symptoms (e.g cough, shortness of breath, pleuritic type chest pain, orthoponea) .
Pleural effusions are common and devastating complication of advanced malignancies, e.g., lung and breast, pleural effusion, associated with carcinoma of breast is the most common clinical and radiological finding.
Thromboembolic disease has long been recognized as a complication of cancer. Patients with breast cancer are at risk of various thromboembolism like all patient with cancer. Microscopic tumor emboli are not also rare in those patients..
Treatment options of breast cancer including surgical resection, radiation therapy, and chemotherapy often produce thoracic abnormalities. In this study we evaluated the variety of thoracic manifestations that can be encountered by radiologists involved in the treatment of patients with breast cancer.
Breast cancer is the most common cancer and the second principal cause of cancer deaths in women worldwide [6.7]. For women with symptomatic breast cancer, prolonged delay, defined arbitrarily as an interval greater than 3 months from first detection to time of diagnosis and treatment has been shown to be associated with increased tumor size [8,9] and more advanced stage of disease  and with poor long-term survival11]. Although there is strong evidence suggesting that older women in the developed countries are more likely to delay their presentation with breast cancer, [12,13], there is data suggesting that factors related to women's knowledge and beliefs about breast cancer and its management may contribute significantly to medical help-seeking behaviors [14,15,16].
Breast cancer presents most commonly as a painless breast lump and a smaller proportion with non-lump symptoms. For women to present early to hospital they need to be "breast aware"; they must be able to recognize symptoms of breast cancer through routine practice of practicable screening. At the present time, routine mammography cannot be recommended in developing countries due to financial constraints and the lack of accurate data on the burden of breast cancer in these countries.
Sudan, breast cancer:
In Sudan, breast cancer is the most common malignancy in women. From the few, limited sources we can indicate that breast cancer in Sudanese women is in the rise. Unfortunately, 80-85% of these women present with a late stage. Superstition, local healers, poverty, illiteracy and ignorance, lack of an effective health education and screening system, and poor distribution of the limited medical resources contribute to this late presentation and death. The high morality as a result of late diagnosis gives the disease and the medical institutions a bad reputation that in turn deters others from seeking medical help early.
The female breast is made up mainly of lobules (milk-producing glands), ducts (tiny tubes that carry the milk from the lobules to the nipple), and stroma (fatty tissue and connective tissue surrounding the ducts and lobules, blood vessels, and lymphatic vessels). Most breast cancers begin in the cells that line the ducts (ductal cancers). Some begin in the cells that line the lobules (lobular cancers), while a small number start in other tissues.
Breast cancer can be presented as:
Signs and symptoms of breast cancer include a lump in the breast, which is the most common first sign:
The woman usually finds the lump.
Sometimes the lump is seen on a screening mammogram before it can be felt.
The lump is present all the time and does not get smaller or go away with the menstrual cycle.
The lump may feel like it is attached to the skin or chest wall and cannot be moved.
The lump may feel hard, irregular in shape and very different from the rest of the breast tissue.
The lump may be tender, but it is usually not painful.
Pain is more often a symptom of a non-cancerous (benign) condition, but should be checked by a doctor. 
Late signs and symptoms occur as the cancer grows larger or spreads to other parts of the body, including other organs. 
Investigations of suspected breast cancer include mammography, ultrasound, breast needle biopsy and other tests such as breast magnetic resonance imaging.
The main stages are:
Where available, imaging studies may be employed as part of the staging process in select cases to look for signs of metastatic cancer. However, in cases of breast cancer with low risk for metastasis, the risks associated with PET scans, CT scans, or bone scans outweigh the possible benefits, as these procedures expose the patient to a substantial amount of potentially dangerous ionizing radiation. [21,22]
Management of breast cancer by:
Surgery: Standard surgeries include:
On the other hand, thorax is the part of the body between the neck and abdomen; the chest. It is separated from the abdomen by the diaphragm. The walls of the thorax are formed by pairs of ribs, attached to the sides of the spine and curving toward the sternum. The cranial pairs of ribs are attached to the sternum, the next few connect with cartilage connected to the sternum and often the last one or two (the floating ribs) are unattached distally. The cavity of the thorax is divided by a thick partition, the mediastinum. The principal organs in the thoracic cavity are the heart with its major blood vessels, and the lungs with the bronchi. The trachea enters the thorax to connect with the lungs, and the esophagus travels through it to connect with the stomach caudal to the diaphragm.
Both lungs are divided into lobes, the gross functional subunits of each lung are called segments and have a close relation with the segmental bronchi. The right lung comprises 10 segments: 3 in the right upper lobe (apical, anterior and medial), 2 in the right middle lobe (medial and lateral), and 5 in the right lower lobe (superior, medial, anterior, lateral, and posterior). The left lung comprises 8 segments: 4 in the left upper lobe (apicoposterior, anterior, superior lingula, and inferior lingula) and 4 in the left lower lobe (superior, anteromedial, lateral, and posterior). The lungs are covered by the visceral pleura, which is contiguous with the parietal pleura as it reflects from the lateral surfaces of the mediastinum. The visceral pleuron forms invaginations into both lungs, which are called fissures. There are 2 complete fissures in the right lung and 1 complete fissure with an incomplete fissure in the left; these separate the different lung lobes. The pleura also forms the pulmonary ligament, which is a double layer of pleura that extends caudal along the mediastinum from the inferior pulmonary vein to the diaphragm.
There is a broad spectrum of thoracic manifestations in patients with breast cancer. The radiologist must be familiar with the appearance of the chest wall after various surgical treatments for breast cancer. Treatment-related complications are variable and include surgery-related complications such as seroma and infection, radiation-induced pneumonitis, and chemotherapy-induced complications such as cardiotoxicity, pneumonitis, and infection. Diagnosis of these complications is not difficult after consideration of the patient’s clinical history, even though the imaging features are nonspecific. The thorax is a common site of breast cancer metastasis. The manifestations of metastasis are variable and include local or regional recurrence, bone metastasis, spinal cord compression, solitary or multiple pulmonary nodules with or without cavitation, an airspace pattern, endobronchial metastasis, and metastasis to the mediastinal lymph nodes, pleura, or pericardium. Familiarity with the radiologic appearances of thoracic metastases from breast cancer allows proper image interpretat .
The most common thoracic manifestations include local and regional recurrence and metastases, which constitute the most common sites of soft-tissue recurrence of breast cancer. The most common distant sites of metastasis are bone and lung. Intrathoracic metastasis from breast cancer commonly involves the lungs, pleura, mediastinum, and airway .
Local recurrence is the reappearance of tumor at the surgical site. Regional recurrence is defined as the appearance of metastases in the lymph nodes that drain the breast, including the supraclavicular, axillary, and internal mammary nodes. The likelihood of local or regional recurrence is greater in patients who have not received postoperative radiation therapy and in those with large primary tumors, positive margins, multiple cancers at the time of initial presentation, and positive lymph nodes [26,27].
Local recurrence is evaluated primarily with physical examination that includes the surgical site, axilla, supraclavicular fossa, and neck. Mammography is an important adjunct to physical examination in the follow-up of breast cancer patients who have been treated with BCS. However, the ability of mammography to help detect local recurrence is compromised by the presence of postoperative distortion and the increased density of the irradiated breast. Mammography is able to help detect only two-thirds of recurrences in postlumpectomy patients . Rissanen et al  evaluated the usefulness of mammography and US for the diagnosis of local recurrence following mastectomy. The sensitivity of US was 91%, whereas the sensitivities of clinical examination and mammography were 79% and 45%, respectively.
CT has been shown to delineate more clearly than physical examination the extent of recurrent breast carcinoma following mastectomy and is of great value in treatment planning [29,30,31]. CT findings in local recurrence include focally thickened skin to a depth greater than 1 cm (soft-tissue window); dense, mass-like accumulation of soft tissue within the subcutaneous fat; and obvious masses within the chest wall muscles. Contour irregularities or CT inhomogeneity of the muscle can indicate recurrence . Sometimes residual muscle also mimics local recurrence.
Lindfors et al  reported that in most patients CT not only allowed more accurate determination of disease extent than did physical examination, but also demonstrated additional, clinically unsuspected disease in 49% of patients. The most common site of clinically unsuspected disease was the internal mammary nodal chain.
The normal internal mammary lymph nodes are less than 5 mm in diameter and lie within 3 cm of the edge of the sternum, in the fat and areolar tissue on the endothoracic fascia of the spaces between the costal cartilages. Metastasis to internal mammary lymph nodes is not easily detected at physical examination, mammography, or US because of overlying muscular, cartilaginous, and osseous structures. Normal internal mammary nodes are not routinely identified at CT. Therefore, a lymph node greater than 6 mm in diameter visualized at CT in a patient with breast cancer can suggest malignant lymphadenopathy .
Lymphatic drainage to the internal mammary nodal chain is an important pathway of disease spread, both at the time of initial diagnosis and following primary treatment of breast cancer. The prognosis for patients with internal mammary and axillary node metastases is significantly worse than that for patients with only axillary node disease, which suggests that the internal mammary nodal chain is a channel for more widespread dissemination of disease [33,34].
Metastasis of breast cancer to intrathoracic nodes occurs frequently. An autopsy series by Thomas et al  of women who had died of disseminated breast cancer revealed metastatic involvement of intrathoracic lymph nodes in 71% of cases. Lymph node involvement was more extensive in the mediastinum ipsilateral to the primary breast cancer than in the contralateral mediastinum .
CT has been the main modality used to evaluate intrathoracic nodes, but this imaging technique, in which size is the main criterion used to assess nodal status, is limited by its poor sensitivity.
Development of a solitary pulmonary nodule in patients previously treated for breast cancer may represent something other than recurrent disease. Casey et al  found that 52% of breast cancer patients presenting with a solitary pulmonary nodule had primary lung cancer, 43% had metastatic breast cancer, and 5% had benign lesions. Histologic confirmation is necessary for appropriate staging and treatment.
Multiple pulmonary nodules are common findings in lung metastasis from breast cancer . They occur by means of hematogenous tumor spread. In general, metastatic lesions are spheric or ovoid, vary in size, are sharply marginated, and are located mostly in the periphery of the lung) [37,38,39,40]
Cavitation of metastatic nodules is rarely seen at radiography. However, cavitation in metastatic adenocarcinoma (including breast cancer) is frequently encountered at CT [40,41]. Chemotherapy occasionally induces cavitation in metastatic pulmonary nodule s. The exact mechanism is usually difficult to determine, but the cause is presumed to be either tumor necrosis or a check-valve mechanism that develops by tumor infiltration of bronchial air-containing structures .
In an autopsy series by Connolly et al  of women who had died of disseminated breast cancer, 83% of patients had pulmonary lymphangitic metastases. Kreisman et al43] reported that lymphangitic metastasis was the most frequently observed pulmonary manifestation in patients with thoracic metastases from breast cancer.
Radiologically demonstrable lymphangitic disease is rare compared with the results of large autopsy series. Radiographic findings in lymphangitic metastasis include reticular or reticulonodular interstitial markings, usually with an irregular contour, and thickening of the interlobar septa (Kerley B lines). Bilateral involvement is more common than unilateral lymphangitic spread . However, unilateral involvement occurs more frequently in breast cancer than in other malignancies [35,44].
High-resolution CT is the most sensitive imaging tool for the detection of lymphangitic metastasis. High-resolution CT shows irregular, sometimes nodular thickening of the interlobar septa and the peribronchovascular sheaths and thickening of the core structures in the central portions of the secondary pulmonary lobules .
Breast cancer is the most common tumor causing endobronchial metastasis, accounting for approximately 63% of all such metastases . There are five possible routes for the pathogenesis of endobronchial metastasis: (a) mediastinal or hilar metastasis with bronchial extension, (b) parenchymal metastasis with bronchial involvement, (c) bronchial aspiration of tumor cells, (d) direct lymphatic metastasis to the bronchial wall, and (e) direct hematogenous metastasis to the bronchial wall . Endobronchial metastasis has the same clinical and radiologic appearance as primary bronchogenic carcinoma. Affected patients present with symptoms such as cough or dyspnea with or without radiologic findings of pulmonary nodules, pneumonitis, atelectasis, pleural effusion, and hilar lymphadenopathy. Although CT may not always demonstrate intraluminal lesions, it may reveal other manifestations of metastatic breast cancer such as hilar or mediastinal lymphadenopathy and single or multiple pulmonary metastatic deposits .
The pleura is a frequent target of metastatic breast cancer. Thomas et al  found metastases to the visceral and parietal pleura in 75% and 50% of cases, respectively. Pleural effusion is the most common manifestation of pleural metastasis in patients with breast cancer. The effusion is more commonly unilateral and ipsilateral to the primary tumor . Thomas et al  explained that the laterality of pleural metastasis is due to lymphatic dissemination in breast cancer: The cancer spreads from the ipsilateral internal mammary nodes by lymphatic communications, and the lung, pleura, and pericardium become secondarily involved by lymphatic communications from metastatic mediastinal nodes. It would be expected that ipsilateral mediastinal nodes would become involved sooner than contralateral nodes because of the delay in tumor embolization or permeation across the mediastinum.
Chest radiography, CT, and US usually demonstrate free or loculated pleural effusion without any specific features in the effusion itself. Thoracentesis combined with pleural biopsy provides a diagnosis of malignant effusion. The fluid is usually an exudate with a glucose concentration lower than the corresponding serum value. The fluid may be bloody and contain a variable number of malignant cells. The size of the effusion may help suggest metastatic disease, with larger effusions more likely to be malignant .
Pleural nodularity, irregular pleural thickening, and plaque are less common findings in pleural metastases and rarely occur without an accompanying pleural effusion .
Cancer is recognized as an independent and major risk factor for venous thromboembolism (VTE)[49,50]. According to available data and to population-based studies, cancer is in fact associated with a 4.1-fold greater risk of thrombosis [51,52]. Also, VTE is associated with a high potential of morbidity and mortality in cancer patients [53,54] it is indeed the second leading cause of death in cancer patients . Occurrence of VTE has been proven to increase the likelihood of death in cancer patients by two- to sixfold [53,55].
Pneumonia is an inflammatory condition of the lung affecting primarily the small air sacs known as alveoli [56,57] Typically symptoms include some combination of productive or dry cough, chest pain, fever, and trouble breathing. Severity is variable. It is a major risk factor for morbidity and mortality in patients with breast cancer.
Radiation therapy is widely used in postoperative breast cancer patients to reduce the risk of locoregional recurrence and to decrease the tumor volume in advanced cases [58,59,60]. Radiation pneumonitis usually occurs approximately 4–12 weeks after completion of radiation therapy. Initially, diffuse haziness develops in the irradiated region. Patchy consolidations appear and coalesce to form an area with a relatively sharp edge that conforms to the shape of the treatment portals. These manifestations may gradually clear or completely disappear but may lead to fibrous changes, which take 6–24 months to evolve but usually remain stable after 2 years .
The radiographic changes in radiation pneumonitis are generally confined to the field of irradiation, although there have been reports of extensive radiation pneumonitis occurring outside the treatment portals [62,63]. There are three radiation portals that induce radiation pneumonitis in breast cancer patients: the tangential beam portal, the supraclavicular portal, and the internal mammary portal .
Tangential beam radiation portals are frequently used to irradiate the chest wall. Typically, a 1.5–3-cm strip of underlying peripheral lung is included in the irradiated filed. Radiation pneumonitis occurs in the peripheral lung anterolaterally, has a characteristic shape, and is better visualized at CT than at chest radiography.
The supraclavicular portal is positioned with the inferior border at the first or second intercostal space. The medial border is 1 cm across the midline, extending upward and following the medial border of the sternocleidomastoid muscle to the thyrocricoid groove. The lateral border appears as a vertical line at the level of the anterior axillary fold . When supraclavicular portals are used, radiation-induced change occurs in the apex of the lung; the resulting lesions are similar to those seen in pulmonary tuberculosis .
Internal mammary lymph nodes are irradiated with an anteroposterior or oblique beam angle to match the medial tangential beam portal. The medial border of the internal mammary field is the midline. The lateral border is usually 5 cm lateral to the midline, the superior border abuts the inferior border of the supraclavicular field, and the inferior border is at the xiphoid process . When internal mammary portals are used, radiation-induced change occurs in the paramediastinal region .
When pulmonary areas of increased opacity are seen at follow-up radiography in patients treated with radiation therapy, the differential diagnosis includes radiation pneumonitis, local recurrence, lymphangitic tumor spread, and infectious pneumonitis [66,67].
High-dose chemotherapy with autologous bone marrow transplantation is now being widely used to treat advanced or metastatic breast cancer. Pulmonary complications after bone marrow transplantation include infections, pneumonitis caused by chemotherapy or radiation therapy, diffuse alveolar hemorrhage, and idiopathic interstitial pneumonitis. Pulmonary drug toxicity occurs in 31%–58% of patients who undergo high-dose chemotherapy with autologous bone marrow transplantation[68,69]. Dyspnea, cough, and fever are also common and, on average, develop 60–70 days following bone marrow reinfusion. Chest radiographs are normal in many of these patients, although CT reveals parenchymal abnormalities in 3%–65% of cases. The most common CT manifestations of pulmonary drug toxicity are peripheral ground-glass attenuation or consolidation that occasionally appears nodular or mass-like .
There are previous related studies for example the following:
A study conducted in Turkey by Ipek (2013)  to determine the most common clinical and radiological manifestations in patients with Breast cancer. The patients with breast cancer who had pulmonary complaints and radiologic abnormalities observed during oncology follow-ups were hospitalized, and investigated in clinics of chest disease. Pulmonary lesions were classified into 2 groups; Group I: malignant lesions due to metastasis of breast cancer, and Group II: nonmalignant lesions. The results showed that mean age of the patients was 52.4±14.8 years, range (28-93) years. Thirty- four patients were previously diagnosed with unilateral and 2 patients with bilateral ductal breast carcinoma. Twenty seven percent (n=10) of the patients were smokers (mean 10.7±6.81 pack-years). The mean time between the detection of breast cancer and the manifestations of pulmo-nary symptoms was 57.02 ± 53.83, range (3-180) months). The most common radiological abnormality was pleural effusion (n=23; 63.9 %). Twenty-seven (75 %) patients had malignant (Group I), and 9 (25 %) patients had nonmalignant (Group II) pulmonary lesions. Malignant histopathology (n=27) was established by pleural fluid cytology in 13 (48.1 %), fiber optic bronchoscopy in 8 (29.6 %), pleural biopsy in 4 (14.8 %), CT guided transthoracic needle aspiration biopsy in 1 (3.7 %) and thoracotomy in 1 (3.7 %) patient, respectively. Mean time interval between the diagnosis of breast cancer and the detection of malignant pleural effusion was 69.91±64.21 (3-180) months. Nine (25 %) patients had nonmalignant pulmonary lesions including pneumonia in 3 (33.3 %), pulmonary thromboembolism and DVT in 3 (33.3 %), tuberculosis in 2 (22.2 %) and pulmonary fibrosis in 1 (11.1%) patient. In conclusion; pulmonary manifestations of breast cancer are most commonly related to metastases and can be observed in long time after the diagnosis of breast cancer. Besides, these nonmalignant reasons should be kept in mind and histopathologic confirmation should be made.
A study conducted in India by Patil, et al (2011- 2014)  on carcinoma breast related metastatic pleural effusion. The results showed that during the study period, 9 patients with past history of carcinoma breast were included with a mean age of 46.8 years. Presented with recurrent pleural effusion whose cause remained unexplained after extensive biochemical and cytological analysis. Primary malignant tumor of the breast was localized on the left side in 7 cases, and right sided in 2 cases. Histological evaluation of pleural biopsy yielded the diagnosis of metastatic deposits from primary ductal carcinomas in 6 cases and lobular carcinomas of the breast in 3 cases. Pleural effusion was present in all the cases, localized on the left side were 5 cases, on the right side in 2, and on both sides in 2 cases. In total, 7 cases showed pleural involvement on the same side as the primary breast cancer and 2 cases showed bilateral involvement. Pleural fluid was hemorrhagic in all the cases, with pleural fluid hematocrit <50% of peripheral blood. Pleural fluid was negative for malignant cells on three consecutive occasions. The thoracoscopic view revealed thickened, no smooth pleura which was hyperemic in nature and bled on touch. Pleural nodules of varying sizes grossly studded on both the pleurae with/without the involvement of diaphragmatic pleura. At places, these conglomerated pleural nodules forming "grape like pattern". In some cases, isolated distribution of nodules on the parietal pleura mimicking that of "candle wax droplets". Nodules were fragile and bled on touch. Thin fibrinous pleura-parenchymal adhesions were also noted, in some cases. The diaphragmatic surface was involved in 5 cases. Pleurodesis was done in all the patients. In conclusion; carcinoma of breast related pleural effusion is a common condition encourage in respiratory medicine and oncology. Thoracoscopic guided pleural biopsy is an effective and safe technique in patients with undiagnosed pleural effusion it is not only give an accurate diagnosis but also gives a high degree of relationship between theoracoscopic appearance and primary disease or tumor classification.
A retrospective comparison analysis (2006) (72) was performed on 43 Pulmonary lymphangitic carcinomatosis (PLC) patients with pathologic diagnosis and 46 patients with other pulmonary interstitial diseases with clear etiology in the first affiliated hospital of Sun Yat-sen University within the past decade. The results showed that in PLC group, 20 patients were found with primary lung cancer; 23 patients were found with primary non-pulmonary carcinoma: 9 cases of breast cancer, 8 cases of large intestinal carcinoma, and 6 cases of gastric carcinoma. The changes of imaging included linear and radiating appearances from the hilum to the outer part even extending to the pleura with nodules, ground-glass opacity of the lung. Enlargement of lymph nodes in mediastinum was present in 51.2% (22/43) and that in pleural effusion was present in 53.5% (23/43) of patients. Extrapulmonary manifestations (metastasis) included 19 cases (44.2%) of lymph nodes to the supraclavicular region, axillary fossa, and post-peritoneal region, 15 cases (34.9%) to the pleura, 9 cases (20.9%) to the bones, 6 cases (14.0%) to the liver, 3 cases (7.0%) to the pericardium, and 3 cases (7.0%) to the brain. The elevated serum level of CEA was commonly observed (23/43, 53.5%). Respiratory manifestations of PLC, such as coughing, panting, dyspnea, and so on, could not be cured by anti-spasm treatment. The development of PLC was so progressive that 31 patients (72.1%) were followed for only 2-7 months before death. The changes of imaging in other pulmonary interstitial disease group included irregular linear or reticular appearances, enlargement of lymph nodes in the mediastinum and hilum, and extrapulmonary manifestations like pleural effusion were not observed. Respiratory manifestations, such as coughing, panting, dyspnea, and so on, could be cured by anti-spasm treatment. Moreover, the development of PLC was relatively slow. In conclusion PLC often occurs in patients with primary carcinoma in lung, breast and so on. More attention should be paid to the diagnosis of PLC in patients who have pulmonary interstitial lesions and whose respiratory symptoms could not be relieved by anti-spasm treatment and developed progressively. The prognosis of PLC is poor.
To evaluate the thoracic manifestations in Sudanese patients with breast cancer.
- To determine the most common thoracic manifestations those are detected clinically among the study population.
- To identify the most common thoracic manifestations those are detected radiologically among the study population.
Study type: This is a prospective descriptive cross-section hospital-based study.
Study duration: The study was carried out during the period from January to September 2017.
Study area: The study was conducted at specialized clinic of breast cancer, Respiratory Department in Alshaab Teaching Hospital and Oncology Units at Alamel Tower.
Specialized Clinic of breast cancer: it is specialized clinic for surgery and breast cancer, located in Khartoum, Isbitalia Street.
-Respiratory Department in Alshaab Teaching Hospital, which is a hospital- public health care organization at Khartoum, Sudan, in 1962 joined the Section of Cardiology, founded by Dr. Alnoor Abdul-Majid Hospital and thus expanded new sections of the heart and chest surgery (cardiothoracic), X-ray.
- Oncology Units at Alamel Tower: It provides treatment of the cancer patients by using radiotherapy, chemotherapy and hormone therapy. It is a diagnostic centre, giving patients social and psychological services.
Study population: All patients with breast cancer attended specialized clinic of breast cancer, Respiratory Department in Alshaab Teaching Hospital, and Oncology Unit at Alamel Tower during the study period.
Inclusion criteria: The inclusion criteria of this study were all patients, both sexes attended the study area during the study period with breast cancer associated with thoracic abnormalities, which confirmed clinically and radiologically by chest X-ray and CT chest.
Exclusion criteria: the following were excluded from the study:
-Patients with rather than thoracic manifestations (e.g., bone metastases, brain metasteses…. etc).
-Patients refused to participate in the study.
Sample size: Total coverage of patients with breast cancer associated with thoracic manifestations, who fulfilling inclusion criteria of the study. It was found to be 70 patients.
Procedure: The X-ray and CT scan were performed for all participants to detect thoracic manifestations and confirm diagnosis.
Data collection tools: The information was obtained by the author with data collection sheet (Appendix 1). The information was validated by clinical and radiological exam results and referring oncologists notes were reviewed to confirm a diagnosis of thoracic manifestations in all patients in the study.
-The proposal of the study was presented to the ethics review committee of the Sudan Medical Specialization Board, Council of Respiratory Medicine for approval.
-Ethical approval was obtained from clinic, center and hospital directors.
-Participants were informed about the purposes and objectives of the study and verbal consent was obtained.
Data management and presentation: Data for each patient was coded for subsequent computer processing and analysis using the Statistical Package for Social Sciences (SPSS), version 21. The results obtained were presented in tables and figures. The level of significance was taken as P < 0.05.
In this study which aimed to evaluate the thoracic manifestations in Sudanese patients with breast cancer, a total of 70 patients with breast cancer were evaluated clinically and radiologically. Out of them 68 (97.1%) were females and 2 (2.9%) were males (Figure 1). The mean ± standard deviation of patient's age was (49.91 ± 18.26) years respectively (Table 1).
Distribution of the study population according to residence showed that, 38 (55.07%) were from Khartoum, while 31 (44.93%) patients from outside Khartoum State (Figure 2).
Figure 3 shows that 27 (38.6%) patients were married, 19 (27.1%) patients were widows, 13 (18.6%) patients were single and 11 (15.7%) patients were divorced.
In this study, most of patients were not smokers, 47 (67.1%), while, 23 (32.9%) patients were smokers (Figure 4).
Table 2 shows the time interval between the diagnosis of primary breast cancer and detection of thoracic manifestations was found to be 1-3 years in half of the study population 35 (50.0%), and
In this study, distribution of study population according to side of breast cancer showed that, 59 (84.3%) patients were with unilateral breast cancer, while, 11 (15.7%) patients were with bilateral breast cancer (Figure 5).
Table 3 shows distribution of the study population according to symptoms of thoracic manifestations, the most common was SOB in 68(97.1%) cases, followed by cough in 59 (84.3%) patients, out of them 38 (64.4%) had productive cough and 21 (35.6%) patients had dry cough, 29 (41.4%) patients suffered of chest pain, fever, weight loss, and hemoptysis which were found in 25 (36.2%), 24 (34.3%), and 11(15.7%) respectively.
In detection of thoracic manifestations of the breast cancer radiologically based on X-ray, the results showed that, pleural effusion was found in 39 (55.7%) patients, nodules in 26 (37.1%) patients, consolidation in 13 (18.6%) patients, Infiltration (lymphangities carcinomatosis) in 7 (10.0%) patients, Cavity in 6 (8.6%) patients and mass in 6 (8.6%), Reticulation in 1(1.4%) patient (Table 4).
In detection of thoracic manifestations of the breast cancer radiologically based on CT, the results showed that, pleural effusion was found in 39 (55.7%) patients, nodules in 26 (37.1%) patients, consolidation in 13 (18.6%) patients, pulmonary embolism in 7 (10.0%) patients, lymphangities carcinomatosis in 6 (8.6%) patients, mass in 5 (7.1%), Cavity in 4 (5.7%) patients and fibrosis in 3 (4.3%) patients (Table 5).
Figure 6 shows that, pleural effusion was found in 39 (55.7%), out of them, 19 (48.7%) developed right sided pleural effusion, 15 (38.5%) developed left sided pleural effusion, and 5 (12.8%) developed bilateral sided pleural effusion,
Figures 7 and 8 show that there was statistically insignificant correlation between presences of nodule and the side of breast cancer among the study population (P. value = 0.735, P. value = 0.735) respectively.
Figures 9 show that there was statistically insignificant correlation between presences of pleural effusion and the side of breast cancer among the study population (P. value = 0.533).
Figure 1: Distribution of the study population according to gender.
Table 1: Mean age of the study population.
Figure 2: Distribution of the study population according to residence.
Figure 3: Distribution of the study population according to marital status (n = 70).
Figure 4: Distribution of the study population according to smoking.
Table 2: Distribution of the study population according to time interval between diagnosis of Brest cancer and detection of thoracic manifestations (n = 6).
|Time Interval (Year)||Frequency||Percentage|
Figure 5: Distribution of the study population according to side of breast cancer (n = 70).
Table 3: Distributions of the study population according to respiratory symptoms (n = 70).
Table 4: Distributions of the study population according to detection of thoracic manifestations of the breast cancer radiologically, based on X-ray (n = 70).
Figure 6: Distribution of the pleural effusion (n = 39) according to its side among the study population.
Table 5: Distributions of the study population according to detection of thoracic manifestations of the breast cancer radiologically, based on CT (n = 70).
Figure 7: Correlation between presences of nodule and the side of breast cancer among the study population (Based on X-ray) (n = 70).
Figure 8: Correlation between presences of nodule and the side of breast cancer (Based on CT) among the study population (n = 70).
Figure 9: Correlation between presences of pleural effusion and the side of breast cancer (Based on CT) among the study population (n = 70).
Breast cancer takes the first place among cancers with metastatic spread to lung and pleura. Interestingly, pulmonary metastasis can occur a long time after the diagnosis of breast cancer. Moreover, non-malignant pulmonary pathology and chemoradiotherapy related problems can also occur. Consequently, in these patients the most important point is the clear descriptions of the pulmonary problems.
In this study females were predominant 68 (97.1%) than males 2(2.9%).
The mean age was (49.91 ± 18.26) years. This compared with that found in previous study  which reported that the mean age of their study population was 52.4±14.8 years.
In this study, most of the patients were not smokers, 47 (67.1%), while, 23 (32.9%) patients were smokers. This results in contrast with previous studies which reported that increased rate of pulmonary metastases among smokers. [73,74] This difference can be explained by the fact that most of our patients were females and smoking in female is a stigma in our community. [73.74]
The time interval between the diagnosis of primary breast cancer and detection of thoracic manifestations was found to be 1-3 years in half of the study population 35 (50.0%), and
In this study, 59 (84.3%) patients were with unilateral breast cancer, while, 11 (15.7%) patients were with bilateral breast cancer. Our results were supported by that found in previous study done by Ipek, et al., 34 patients were previously diagnosed with unilateral and 2 patients with bilateral ductal breast carcinoma. Also in other previous study by Patil, et al (2011- 2014)  reported that primary malignant tumor of the breast was localized on the left side in 7 cases, and right sided in 2 cases.
The most common symptoms of thoracic manifestations were SOB in 68(97.1%) cases, followed by cough in 59 (84.3%) patients, out of them 38 (64.4%) had productive cough and 21 (35.6%) patients had dry cough, 29 (41.4%) patients suffered of chest pain. The remaining symptoms are fever, weight loss, and hemoptysis which recorded in 25 (36.2%), 24 (34.3%), and 11(15.7%) respectively. These findings compared with that reported in previous literature; Dyspnea, cough and chest pain were the most com¬mon (58.3 %, 55.6 %, 36.1 %, respectively).
In detection of thoracic manifestations of the breast cancer radiologically based on X-ray, pleural effusion was found in 39 (55.7%) patients, nodules in 26 (37.1%) patients, consolidation in 13 (18.6%) patients, Infiltration in 7 (10.0%) patients, Cavity in 6 (8.6%) patients and mass in 6 (8.6%), Reticulation in 1(1.4%) patient. While detection radiologically based on CT, the results showed that, pleural effusion was found in 39 (55.7%) patients, nodules in 26 (37.1%) patients, consolidation in 13 (18.6%) patients, pulmonary embolism in 7 (10.0%) patients, lymphangitis carcinomatosis in 6 (8.6%) patients, mass in 5 (7.1%), Cavity in 4 (5.7%) patients and fibrosis in 3 (4.3%) patients. These findings were compared with that found in previous studies which all confirmed that pleural effusion was the most common radiological manifestation in patients with breast cancer. [70,71]
Pleural effusion was found in 39 (55.7%), out of them, 19 (48.7%) developed right sided pleural effusion, 15 (38.5%) developed left sided pleural effusion, and 5 (12.8%) developed bilateral pleural effusion. This results somewhat agreed with that found in previous study conducted by Patil, et al (2011- 2014)  they mentioned that pleural effusion was present in all the cases, localized on the left side were 5 cases, on the right side in 2, and on both sides in 2 cases. In total, 7 cases showed pleural involvement on the same side as the primary breast cancer and 2 cases showed bilateral involvement.
In this study there was nonmalignant pulmonary lesions were found included pneumonia in 13 (18.6%) patients, compared with previous study conducted in Turkey, they found only 3 cases of pneumonia. Pulmonary thromboembolism in 7 (10.0%) patients. Breast cancer can be determined as a risk factor. Patients with breast cancer are at risk of venous thromboembolism like all patients with cancer. [49,50,51] Tuberculosis in 2 (2.9 %) patients (in 1 patient there was a cavity in the right upper lobe with sputum positive result, so started antituberculosis drug, the other one had sputum negative with cavitary lesions, so was given treatment for tuberculosis). These 2 patients with tuberculosis can be evaluated as coincidental cases.
There was statistically insignificant correlation between presences of nodule, pleural effusion and the side of breast cancer among the study population (P. value = 0.735, P. value = 0.735) respectively.
Finally, in our study we used X-ray and CT as diagnostic tools to detect thoracic manifestations of breast cancer, although X-ray technology has advanced rapidly in recent years with the introduction of high-resolution digital X-rays, the smallest nodule size it can detect is limited to 1 to 2 cm. The false-positive rate ranges between 10 and 20 percent, in spite of its low cost, availability and safety. While low-dose spiral computer tomography (LDCT) detect nearly six times as many nodules as traditional X-ray radiography. With resolution capabilities under less than 1 cm and the ability to generate 3-D views of the lungs, LDCT generated excitement as a high-quality substitute to X-rays.
Some potential limitations of our study should be considered.
-Although subjects were selected consecutively when they fulfilled the inclusion criteria, such a convenience sample might have introduced a bias.
-We evaluated small sample in the present study. Nevertheless, our study should be repeated with larger samples.
According to findings from this study we concluded that:
-The thoracic manifestations in Sudanese patients with breast cancer were pleural effusion, metastases, pulmonary embolism, lymphangitis carcinomatosis, masses, cavity and fibrosis.
-The most common thoracic manifestations detected clinically among the study population were shortness of breath, cough and chest pain.
-The most common thoracic manifestations detected radiologically among the study population were pleural effusion and metastases.
-Raise community awareness about breast cancer and its thoracic manifestations to seek medical advices early.
-Periodic radiographic controls should be performed, which would provide early recognition of pulmonary lesions and information about the change in size of any pulmonary nodules mass which were present on previous radiographs.
-Availability of chest X-ray and CT scan in oncology clinics and peripheral centers to detect thoracic manifestations early.
-Cooperation between radiologist, oncologist and respiratory physicians, so as to approach to early diagnosis, treatment and avoidance of thoracic manifestations.
-Further studies with large sample size to detect more thoracic manifestations related to breast cancer.
-Advanced technology should be used routinely to detect thoracic manifestations due to breast cancer.
-Palliative care team should be trained and contributed in treatment of thoracic manifestations patients.
Gender: Male _____ Female __________
Residence: Khartoum _____ Outside Khartoum__________
Marital status: Single _____Married _____ Divorced ___ Widow _______
History of smoking: Yes _____ No __________
Time of detection of breast cancer (months): ______________
Time interval between diagnosis of breast cancer and detection of thoracic manifestations (year): >1___ 1-3 ____ 4-6 _________
Cough: Productive ______ Dry ______
Shortness of breath: yes ______ No ______
Fever yes ______ No ______
Chest pain yes ______ No ______
Weight loss yes ______ No ______
Haemoptisis yes ______ No ______
Radiological manifestations based on X-ray:
Effusion __________ Nodules____: Unilateral________ Bilateral___
Consolidation ______ Cavity _________ Mass _____ Infiltration____
Radiological manifestations based on CT;
Effusion __________ Nodules____: Unilateral________ Bilateral___
Consolidation ______ Cavity _________ Mass _____
Infiltration (Lymphangitis carcinomatosis) ____
Fibrosis______ Pulmonary embolism _____________