A narrative review of cutaneous manifestations and imaging landmarks of breast cancer

narrative


INTRODUCTION
Breast cancer is the most prevalent form of cancer in the United States, with an estimated 287,850 new cases and 43,250 fatalities in 2022, representing 15.0% of all new cancer cases [1].In actuality, approximately 12.9% of women will develop breast cancer during their lifespan.
Overall survival rates for breast cancer vary a lot from place to place because people from different socioeconomic backgrounds have different access to screening/early detection, treatment, and specialized therapies.About 10.0-15.0% of newly identified breast cancers in high-income countries are already in stage IV (de novo metastatic breast cancer [MBC]) at the time of diagnosis.In middle-and lowincome countries, this number is much higher.High death rates from breast cancer are linked to less access to public cancer centers and less uniform coverage of health care [2].Also, even if they get the best care, about 30.0% of people with early-stage disease will eventually get sick again [3,4].
Breast cancer can emerge on the skin in two ways: directly, as skin metastases or a direct extension of the tumor; or indirectly, as a paraneoplastic disease.Another crucial circumstance is when cutaneous tumors appear in conjunction with a genetic cancer syndrome that increases the chance of breast cancer, such as Cowden syndrome.Slow progress has been made in MBC treatment, and the median survival time has remained constant at three years [4][5][6][7].However, the biological subtype, as well as accessibility to excellent multidisciplinary care and suitable medicines, all have a significant impact on this figure.Individuals diagnosed with MBC who have positive results for the human epidermal growth factor receptor (HER2) and the estrogen receptor (ER) often experience a prolonged survival period of several years [5][6][7].

MATERIALS & METHODS
A comprehensive literature search was conducted utilizing the databases PubMed, Web of Science, Scopus, and Medline.The search strategy included the use of specific term: "breast cancer", "cutaneous manifestation", "mastectomy", "reconstruction after breast cancer", "imaging of breast cancer", "advanced breast cancer", "metastatic breast cancer", "clinical exam in breast cancer", "cutaneous paraneoplastic syndrome", "radiotherapy and chemotherapy in breast cancer", and "breast cancer mortality", as well as their combinations regarding cutaneous manifestations and imaging of breast cancer.We have selected the articles that we consider relevant for our theme from 2000 to the present with a few exceptions that stand out due to the breadth of the studies and the relevance of the data.

RESULTS
We selected 74 studies for our narrative review.Each study was analyzed by one of the authors and chosen to be used in the review through the prism of the importance of the provided data.The authors appreciated the large groups of patients, the studies carried out in several centers, the systematic presentation of the results as well as the innovations brought to the studied field.We excluded non-peer reviewed articles in preprint databases.No restrictions on language or period of publications were applied.Our research efforts were primarily directed towards the examination of randomized controlled trials, meta-analyses, systematic reviews, and observational studies conducted on extensive patient populations.

Imaging of Breast Cancer
Breast cancer imaging is an essential part of breast cancer screening, diagnosis, preoperative/treatment assessment, and follow-up.Magnetic resonance imaging (MRI), ultrasound and are three fundamental modalities used in medical imaging, each with distinct advantages and constraints.New technologies have also allowed each modality to improve on its shortcomings.Imaging-guided biopsies provide accurate breast cancer diagnosis with low complication rates.
Imaging for breast cancer is divided into two primary categories: screening and diagnostic.The objective of screening mammography (or other imaging modality) in the healthy, asymptomatic female population is to detect undiagnosed cancer and treat it at an earlier stage before it manifests symptoms.Due to the fact that only a small percentage of breast cancers are detectable solely by clinical breast evaluation and the absence of a specific laboratory biomarker for breast cancer, imaging is the cornerstone of early detection [8].Even though everyone agrees that the breast cancer screening program is helpful, no one can agree on the beginning age, ending age, or amount of time between screenings [9].Different countries and organizations, such as the American Cancer Society, the American College of Radiology (ACR), and the European Commission, have come up with different guidelines, but most of them say that screening should start when a woman is between 40 and 50 years old and continue until she is 75 years old or until she has about 10 years left to live [9][10][11].
Diagnostic breast imaging, on the other hand, is for people who have symptoms or who have had an abnormal physical exam or abnormal first imaging (mostly from abnormal breast screening test memories).According to ACR's criteria for appropriateness, if a woman has a palpable finding, ultrasound is the first choice for patients younger than 30 years old, while mammography is the first choice for patients 40 years or older.In both cases, the next step depends on the results of the first investigation [12,13].For women between the ages of 30 and 39, mammograms or ultrasound could be the first screening method of choice.
The cornerstone of breast imaging, both for screening and diagnostic reasons, is mammography.Each breast is photographed in the usual medio-lateral oblique and craniocaudal perspectives during a mammogram, which is a 2D X-ray imaging of the breast.The preferred screening method for symptomatic women 40 years of age and older is mammography, which is also used as the initial diagnostic test [14].Breast calcifications are best discovered by mammography and may go undetected on ultrasound and MRI [15].They can be a marker of ductal carcinoma in situ (DCIS) and invasive malignancy.Additionally, mammography shows panoramic views of both breasts, enabling objective comparisons to the contralateral breast and to various time periods, as well as the identification of asymmetries, architectural anomalies, and spiculated lesions that may be hidden by other imaging modalities [16].
In breast imaging, the United States is a crucial supplementary technique to mammography.It enables realtime, dynamic examination that can help detect minor signs of malignancy and allow for direct assessment of the precise site of a patient's complaints (such as palpable findings, nipple discharge, and discomfort) [17].Cystic and solid lesions may be consistently distinguished using ultrasound, and the solid lesions can be classified as benign or malignant using BI-RADS descriptors.As thick breasts might hide lumps or cancer on a mammography, it can be utilized as a comprehensive screening technique in individuals with dense breasts.With minimal radiation risk, the United States is the first imaging modality of choice for patients under 30 with palpable abnormalities as well as symptomatic pregnant and lactating individuals [13,17].Since ultrasound is the primary recommended technique of breast biopsy, it may be used to examine abnormalities observed on other modalities such as mammography and MRI and enables for biopsy of the findings [17].The ideal way to check the axilla is also with ultrasound since, because of its elevated placement, it frequently does not fit entirely inside the field of view on mammography.
Breast MRI is the most accurate tool we have for diagnosing breast problems with imaging right now.However, it is expensive and hard to get, and it is only good for certain people and clinical situations.Breast MRI is currently used for screening high-risk and some intermediate-risk patients, assessing the extent of disease in a patient with cancer (e.g., to check for multicentricity or invasion of fascia, to find contralateral cancer), and further evaluating clinical or imaging findings (e.g., cancer of suspected breast origin as metastasis in lymph nodes or other organs, with otherwise inconclusive workup with mammogram and ultrasonography) [18].The basic idea behind MRI breast cancer diagnosis is that tumoral neo angiogenesis results in leaky blood vessels that enable contrast to extravasate and provide pictures of cancer "enhancement" [19].When compared to surgical pathology, MRI provides the best correlation of the degree of illness for individuals who have just received a cancer diagnosis, with around 75.0% of malignancies being measured within 1 cm of the pathological size [19].This advantage is especially potent for the identification of DCIS and aggressive lobular cancer.Up to 20.0% of the time, preoperative MRI can identify additional mammographically occult tumors in the ipsilateral and contralateral breasts, changing the patient's therapy [20].
The mainstay of breast cancer diagnosis is imaging-guided breast biopsy.Before biopsies, diagnostic imaging should be obtained as post-biopsy alterations such as hematoma, inflammatory changes, and reactive axillary lymph nodes may make the interpretation of the imaging more challenging.Because it is more readily accepted by patients, less costly, and accessible, ultrasound is the chosen main imaging modality for biopsy [17,21].It also gives radiologists real-time targeting control with nearly no restrictions on the targetable region in the breast.If a mammogram or MRI abnormality necessitates a biopsy and has an ultrasound correlate, an ultrasound biopsy is typically preferred.Otherwise, biopsy under stereotactic (e.g., calcifications), tomosynthesis (e.g., distortions), or MRI (e.g., non-mass enhancement) guidance are also superb options for non-ultrasound-correlated findings.

Cutaneous Manifestations of Breast Cancer
Breast cancer can manifest with skin symptoms.There are a variety of breast cancer cutaneous manifestations (Figure 1).
The most prevalent clinical manifestations of metastatic cutaneous breast cancer lesions will be described.As indicators of breast cancer, erythema gyratum repens (EGR), acquired ichthyosis, dermatomyositis (DM), multicentric reticulohistiocytosis (MRH), and acquired hypertrichosis lanuginose have been identified as paraneoplastic cutaneous dermatoses.Mammary Paget's disease, a condition sometimes accompanied by concurrent breast cancer, and Cowden syndrome, a condition linked to an elevated susceptibility to breast cancer, both have discernible dermatological features.In investigation of newly diagnosed or recurrent breast cancer, it is essential to recognize these distinct cutaneous symptoms.

Breast cancer cutaneous metastases
Breast cancer is the most often seen malignancy in women that exhibits metastasis to the epidermis.The incidence is approximately 20.0%, with one autopsy series reporting that 26.5% of breast cancer patients have metastatic cutaneous lesions, and 23.9% in a meta-analysis [22,23].It was analyzed 724 cases of malignancies with cutaneous metastases that were metastatic [24].In 3.0% of their MBC cases, it was reported cutaneous metastases as the presenting symptom.The most prevalent location for cutaneous breast metastases is the pectoral wall [24,25].Using data from tumor registries, Lookingbill et al. conducted two large retrospective studies and drew several conclusions regarding cutaneous metastases [26,27].Breast cancer was the most prevalent tumor to involve skin, accounting for 23.9% of cases, and 3.5% of breast cancer cases had skin involvement as the presenting indicator.Breast cancer cutaneous metastases are the most common metastases diagnosed by dermatologists [28] (Figure 2).
Breast cancer cutaneous metastasis manifests itself in a variety of forms.It was analyzed the frequency of the most common clinical presentations of cutaneous metastases in a retrospective study [29].Nodules are the most prevalent manifestation, occurring in 80.0% of patients.The nodules are typically non-tender, round or oval, mobile, firm, and gelatinous in consistency.They may be solitary or in groups, typically flesh-colored, but also brown, bluish black, pink, or reddish-brown.Also, they can become ulcerated and infected with poor response to topical treatments [30] (Figure 3).
Histological examination reveals substantial clusters of malignant cells.Other manifestations of breast cancer with cutaneous metastases have been described.The cutaneous Histopathologically, dermal lymphatics are infiltrated by the tumor.Carcinoma en cuirasse, also known as scirrhous carcinoma, is characterized by the presence of dispersed, firm, erythematous, and indurated lesions on the chest wall [31,32].Occasionally, the epidermis may appear yellow and have a fibrotic texture.Histologically, there are a small number of dense neoplastic cells, sometimes arranged in an Indian file pattern.
When there are many skin tumors, the whole body needs to be treated.The consideration of hormone receptor (HR) status and HER2 status is crucial in the treatment of metastatic skin cancers.This is the same way that visceral metastases are treated.Several endocrine drugs can be used to treat a growth that is HR-positive.Chemotherapy is used for skin tumors that are HR-negative and/or are getting worse quickly.HER2directed treatment with or without chemotherapy should be used to treat a tumor that is positive for HER2.External beam radiation therapy can be used to treat skin metastases locally, but it would not be used in places that have already been exposed to radiation because of the total dose.

Paraneoplastic cutaneous dermatoses
There are different skin conditions that can show up as paraneoplastic dermatoses and be linked to breast cancer.Even though it happens rarely, it could help find cancer early.
MRH has reddish-brown lumps and papules that are one to two mm in size and look like "coral beads."They are found on the face and hands [34].The head, ears, wrists, and elbows are also affected.Some of the signs are losing weight, feeling tired, and having a fever.The joint symptoms can include pain in the distal interphalangeal joints of the hands, wrists, shoulders, knees, or hips.This pain can be on one side or both sides.MRH is thought to be caused by reactive macrophages and monocytes, and an underlying tumor could release a factor that could cause a similar histocytic reaction [35].From a histological point of view, there are big, single-nucleated, or multiple-nucleated histiocytes with fine particles in their eosinophilic cytoplasm.One of the cancers most often seen in people with MRH is breast cancer.
EGR looks like wide, colored, circular bands that look like woodgrain or are twisted.It can grow quickly, about one cm per day.Most of it is on the back and arms and legs, but not on the face, hands, or feet.Patients have eosinophilia and have very bad itching.This rash usually gets worse as the cancer gets worse.Most of the time, it shows up between one month and six years before the cancer is found, but it can also happen at the same time or later.The histology shows that there is mild to moderate hyperkeratosis, parakeratosis, spongiosis of the skin, and a lymphocytic infiltrate around the blood vessels.Pathophysiology is not known, but theories include cancerstimulated antibodies that react with cutaneous antigens or the buildup of tumor antibody-antigen complexes in the skin, which causes inflammation [36].EGR goes away when the breast cancer that caused it is treated.Systemic cortisone and topical steroids can be helpful as well with their well-known adverse reactions [37].
The most common skin signs of DM are a heliotrope rash, violaceous, swollen, scaly papules over the knuckles (called Gottron's papules), malar erythema, and erythema or poikiloderma in a "V" pattern on the upper torso (called a "shawl sign").There is weakness in the muscles near the joint.About 20.0% of the time, DM may be a symptom of breast cancer called a paraneoplastic condition.It has been suggested that the immune reaction to tumors can lead to DM and other inflammatory diseases.Also, since DM and cancers often happen at the same time, they could both be caused by the same antigen or carcinogen [36].Most of the time, DM goes away when the breast cancer is treated [39][40][41].
Cowden syndrome, also called multiple hamartoma syndrome, is an example of a cancer syndrome that runs in families and can show up in the skin.There is a higher chance of getting breast cancer (about 20.0% to 50.0%), thyroid tumors, especially follicular and cystic ones, which have a 3.0% to 10.0% lifetime risk, and uterine cancer, which has a 5.0% to 10.0% lifetime risk [42].The condition under consideration is a hereditary cancer syndrome that exhibits autosomal dominance.Its etiology may be attributed to a mutation in the PTEN tumor suppressor gene, located on chromosome 10q22-23.The presence of several face trichilemmomas is a significant dermatological manifestation with clinical relevance.These are small, flesh-colored papules on the face, head, and neck that look like warts and range in size from one to five mm [41].Mucocutaneous diseases also include papillomatous papules on the lips, tongue, gingivae, and oral mucosa, which can look like cobblestones when they stick together.Acral keratoses can also happen.These are bumps on the hands and feet that can be felt or are hyperkeratotic and look like warts.Cancers of the breast, thyroid, and endometrium can happen in people with Cowden syndrome, so knowing about it can help doctors find them [43].

Impact of Mastectomy & Reconstruction Technique
Breast cancer is the prevailing form of cancer among women globally.In the United States, the chance that a woman will get breast cancer in her lifetime is about one in eight [44].Approximately 33.0% of these women will get a mastectomy, either due to the presence of cancer, for aesthetic purposes, or as a result of personal preference.Breast reconstruction will be chosen by half of the women in this subgroup [45].If you decide to have reconstruction after a mastectomy, you will have to make a lot of other choices as well.Some decisions are limited by the patient's anatomy or the skills of the surgeon, but the patient and the healthcare team make decisions about unilateral vs. bilateral surgery, autologous vs. implant-based reconstruction(s), and to some extent, even the timing of reconstruction(s).
When there are so many things to think about when making a number of choices, figuring out how happy the patient is becomes very important.Even though it's clear that rebuilding after a mastectomy has positive effects on a woman's mental health and body image as a whole, there is not much information about how each decision she has to make in this process affects her.
When a breast pathology is found, it is important to think about personal factors like the desire for matching mammoplasty, preventive surgery in the case of non-inherited mutations that cause breast cancer, the time of reconstruction, and the advice of the surgeon [46][47][48].Despite the transformative impact of breast-conserving surgery (BCS) followed by radiation therapy on the management of earlystage breast cancer, patients retain the autonomy to choose among various treatment options according to their own preferences.Due to its good results and ease of use, breast organ protection through breast conserving therapy (BCT refers to BCS typically followed by radiation therapy) is now the treatment of choice in this situation.Despite this, several population-based studies showed that mastectomy is still seen as a real treatment choice and is still picked by many breast cancer patients [49][50][51][52].Early-stage breast cancer care can be thought of as a preference-sensitive setting, where decisions about which treatment choices to choose can change based on what the patient wants [53].
Typical reasons for choosing mastectomy as a treatment include: (a) worries about cancer coming back, (b) the belief that health is more important than keeping the breasts [54], or (c) the imagined effects of BCT, such as the possible side effects of radiation therapy [53,55].
More recently, there has been a rise in the use of skinsparing or nipple-sparing mastectomies with rapid breast reconstruction, which shows a renewed interest in and movement toward mastectomy [56][57][58].Compared to total mastectomy, this treatment gives better results in terms of appearance and quality of life.
Breast cancer treatment has changed a lot over time, and the number of local recurrences after BCT has gone down a lot [59].The effect of mammography screening on disease progression to earlier stages was smaller tumors and less involvement of lymph nodes.This was followed by changes in adjuvant medicines that were made to fit biology of disease.
Post-mastectomy radiation therapy (PMRT) plays a significant role in the local treatment regimen for a substantial number of women diagnosed with breast cancer.When a patient has a mastectomy, they are usually given choices for breast replacement.For people who are candidates for PMRT, it is hard to find the best way to use radiation to get the best oncological results while reducing side effects and getting the best reconstruction results.The way these choices are made keeps changing as surgical and radiation methods get better and more widely used and as more patients with different local recurrence risk profiles get PMRT.
The decision to undergo breast reconstruction represents a significant advancement in the provision of healthcare for those who have had a mastectomy as part of their breast cancer treatment.The impact on the patient's quality of life and mental well-being is substantial.Recent studies say that around 62.0% of women who have had a mastectomy will have reconstruction.Immediate and implant-based repair are also becoming more common [60][61][62][63].Almost one-third of people who have a mastectomy need extra radiation to the chest wall and the lymphatics that drain from it.Several randomized trials and a meta-analysis conducted by the early breast cancer trialists' collaborative group (EBCTCG) have shown evidence that PMRT has benefits in terms of enhancing local control, disease-free survival, and overall survival rates in patients with a higher risk of cancer recurrence [64][65][66][67].But expecting PMRT can cause surgery to be put off or not happen at all.Additionally, it is noteworthy that this condition may have an influence on the patient's physical appearance, overall quality of life, as well as the potential for consequences.A recent revision of EBCTCG meta-analysis showed that PMRT is useful for patients with less advanced diseases.As a consequence of this finding, the national comprehensive cancer network has recommended the use of PMRT for individuals diagnosed with breast cancer who have tumors measuring five cm or less and between one and three positive lymph nodes [68].PMRT has been shown to cause about two to three times as many problems after surgery after an implant or donor repair [69][70][71][72][73][74].Radiation methods are always getting better, with the goal of reducing long-term side effects as much as possible.Integration of reconstruction and PMRT is still hard because of the need to put oncologic outcomes first, improve radiation methods to reduce side effects and try to get a good result from reconstruction.Current data show different chances of complications.This is partly because of differences in how complications are defined and measured, and partly because of differences in how repair is done.

CONCLUSIONS
In conclusion, breast imaging is important for screening, identifying, and assessing breast cancer before and after treatment.Mammography, ultrasound, and MRI each have their strengths and possible weaknesses, as well as new technology developments.The selection of optimal imaging modalities should be contingent upon the patient's risk factors and breast density since breast cancer imaging necessitates a personalized approach rather than a universal solution.Artificial intelligence and personalized screening may become part of everyday professional practice in the future.
There are a lot of different skin conditions that point to breast cancer, either as a sign of recurring disease, undiagnosed breast cancer, or a condition that puts you at a higher risk of getting it.Also, if you notice any of the paraneoplastic skin conditions listed here, you should be suspicious of hidden breast cancer.This will help you get the right diagnosis and treatment for it.
In the end, there is new information about breast surgery after radiation treatment for a mastectomy.Even though reconstruction has been shown to improve quality of life for many women, there are still a lot of complicated factors that affect morbidity and results that make it hard to study and find ways to make real changes.Also, practices vary a lot from one school to the next, which makes things even more complicated.Recent headway has been made with prospective studies that focus on patient-reported outcomes, but the different ways the studies were done, and the different results make it hard to say what the best treatment is.

Figure 1 .Figure 2 .
Figure 1.Ulcer-infiltrative tumor formation, with a crateriform appearance, which completely occupies right breast region (central area is ulcerated, with complete destruction of nipple, showing deep whitish deposits & in periphery, edges of tumor are elevated, with a "lacy" appearance, whitish color, accentuated vascular pattern & numerous hemorrhagic areas) (Source: Emergency Clinical Hospital "Sf Apostol Andrei" Galaţi, First Surgical Clinic.The patient gave her consent to use her personal data and photos by signing the hospitalization form) Figure 2. Ulcer-infiltrative tumor formation located in left mammary region, gray-white in color, with intense hemorrhagic areas (Source: Emergency Clinical Hospital "Sf Apostol Andrei" Galaţi, First Surgical Clinic.The patient gave her consent to use her personal data and photos by signing the hospitalization form)

Figure 3 .
Figure 3. Nodular tumor formation located in left mammary region, whitish in color, with blue areas, increased consistency & with an accentuated vascular pattern (formation is mainly covered by intact skin, except for a small area of ulceration) (Source: Emergency Clinical Hospital "Sf Apostol Andrei" Galaţi, First Surgical Clinic.The patient gave her consent to use her personal data and photos by signing the hospitalization form) Author contributions: RM, ALT, & T-IM: conceptualization; RM & ALT: methodology & writing-review and editing; RM: project administration & funding acquisition; ALT & T-IM: supervision; EN, LR, CM, & MC: validation; LR, VL, & MP: investigation; CM, MC, & FCS: resources; CB, LIC, VL, & OMM: visualization; OMM & MM: software; & T-IM: data curation & writing-original draft preparation.All authors have agreed with the results and conclusions.Funding: APC was paid by the "Dunarea de Jos" University of Galati, Romania.74.FowbleB, Park C, Wang F, et al.Rates of reconstruction failure in patients undergoing immediate reconstruction with tissue expanders and/or implants and postmastectomy radiation therapy.Int J Radiat Oncol Biol Phys.2015;92(3):634-41.https://doi.org/10.1016/j.ijrobp.2015.02.031PMid:25936815